ABSTRACT SUPPLEMENT

2011 ANNUAL SCIENTIFIC MEETING

November 49, 2011Chicago, Illinois

AN OFFICIAL JOURNAL OF THE AMERICAN COLLEGE OF RHEUMATOLOGY

Arthritis & RheumatismV O L U M E 6 3 , N U M B E R 1 0 ( S U P P L E M E N T ) O C T O B E R 2 0 1 1

AMERICAN COLLEGE OF RHEUMATOLOGY ABSTRACT SUPPLEMENT

American College of Rheumatology75th Annual Scientific Meeting

Association of Rheumatology Health Professionals46th Annual Scientific Meeting

November 4-9, 2011 Chicago, IL

Copyright 2011 by the American College of Rheumatology, Atlanta, GAThe printing of the 2011 ACR Annual Scientific Meeting Abstract Supplement was supported by Savient Krystexxa, Inc.

ACR/ARHP 2011 Annual Scientific Meeting Overal Needs Assessment/Practice GapsThe American College of Rheumatology and the Association of Rheumatology Health Professionals are committed to providing comprehensive education to improve the knowledge and performance of physicians, health professionals and scientists. Through evidence-based educational programs, the organization strives to enhance practice performance and improve the quality of care in those with or at risk for arthritis, rheumatic and musculoskeletal diseases. The 2011 annual meeting program has been developed independent of commercial influence. The following groups were involved in the planning process: the ACR Committee on Education; the ACR Annual Meeting Planning Committee; the ARHP Education Committee and the ARHP Annual Meeting Program Planning Committee.

The program is the result of a planning process that identified educational needs to change or enhance the knowledge, competence or performance of rheumatology professionals. The programs content was derived from both needs assessment and practice gap analysis based on professional activities, practice setting, ABIM recertification requirements and physician attributes.

PROGRAM HIGHLIGHTS Educational tracks to help attendees identify content targeted

to them. Tracks include: business of rheumatology, clinical, clinical and research, clinical practice, educators, fellow-in-training, pediatrics, pediatrics and clinical, and research;

Latest science and best-practices presented through peer-reviewed and selected clinical and scientific abstracts, and invited speakers providing clinical, evidence-based and quality focused content;

Diverse formats of education delivery, including: didactic lectures, debates, and interactive sessions, such as poster tours, Meet the Professors and Workshop sessions;

A larger forum for discussion of practical management issues such as the Curbside Consults Ask the Professors session and Medical Aspects lectures;

Extensive learning opportunities in the basic science of rheumatology, an area of the program developed by a subcommittee of US and internationally prominent basic scientists. Offerings include: Basic Science Symposia, State-of-the-Art Lectures, a series of Immunology Updates for the Clinicians, and a Basic Science pre-meeting course;

Clinical management sessions, including the Thieves Market, Curbside Consults Ask the Professors, The Great Debate and the ACR Knowledge Bowl;

A specific pediatric rheumatology track plus content integrated throughout the program designed to provide a high-level educational program to pediatric rheumatologists; and relevant updates to adult rheumatologists;

Formal presentations of new practice guidelines provided to alert the membership and explain, in an open forum, the data supporting the guidelines and propose approaches for implementation;

Over 40 workshops designed to provide hands-on skills training.

For additional details, refer to the session level learning objectives at www.rheumatology.org/annual.

About ACR/ARHP EducationThe American College of Rheumatology and the Association of Rheumatology Health Professionals, a division of the ACR, are organizations of physicians, health professionals and scientists serving members through programs, including education and research. Through these programs, the ACR and the ARHP foster excellence in the care of people with rheumatic and musculoskeletal diseases. The 2011 ACR/ARHP Annual Scientific Meeting programs have been independently planned by the ACR Committee on Education, the ACR Annual Meeting Planning Committee, the ARHP Annual Meeting Program Committee, and the ARHP Clinical Focus Course Task Force.

This program is sponsored by the American College of Rheumatology for educational purposes only. The material presented is not intended to represent the only or the best methods appropriate for the medical conditions being discussed, but rather are intended to present the opinions of the authors/ presenters, which may be helpful to other healthcare professionals. Attendees participating in this medical education program do so with the full knowledge that they waive any claim they may have against the ACR for reliance on any information presented during these educational activities. The ACR does not guarantee, warrant or endorse any commercial products or services.

PROGRAM OBJECTIVESAt the conclusion of the 2011 ACR/ARHP annual meeting, participants should be able to:

identify recent developments in the diagnosis and management of patients with rheumatic diseases

outline new technologies for the treatment of rheumatologic problems

describe potential challenges in the delivery of care to patients with rheumatic diseases and to specify possible solutions

utilize new research data to improve the quality of care of patients with rheumatic diseases

summarize recent rheumatology research findings

Certificates of CME Credit or ParticipationAccreditation Statement: The American College of Rheumatology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Statement of Designation: The ACR designates this live educational activity for a maximum of AMA PRA Category 1 credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

International Physicians: International physicians who register as part of a group and require AMA PRA Category 1 Credit(s), must provide the following information to your tour leader: full name, mailing address, telephone and fax numbers, and e-mail address. The information will be used to verify your meeting attendance.

The American Medical Association has an agreement of mutual recognition of continuing medical education credit with the European Union of Medical Specialties. International physicians interested in converting AMA PRA Category 1 Credit to EACCME credit should contact the UEMS.

Health Professionals: Participants may claim hours to receive a Certificate of Participation for an activity designated for AMA PRA Category 1 Credit(s). For non-CME sessions, attendees may also request a certificate of participation.

Meeting Evaluations, CME Credit/Certificates of ParticipationComputers are available for you to complete your CME/Certificate of Participation application and meeting evaluation form online during the meeting. In addition, you can complete the evaluation and print your certificate after you return home.

If you are an international physician and require a Certificate of Attendance, this is enclosed in your meeting bag. If your country recognizes AMA PRA Category 1 Credit(s) in accordance with AMA PRA requirements, please complete a meeting evaluation and CME application.

Your evaluation of the meeting is very important. The ACR/ ARHP annual meeting planning committees use feedback from attendees to assist in the development of future educational activities; therefore, we encourage you to complete your evaluation and CME/Certificate application online.

ConflICt of IntereSt/DISCloSure StAtementS

As an educational provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), the American College of Rheumatology must ensure balance, independence, objectivity and scientific rigor in all its educational activities. Therefore, all speakers and moderators participating in an ACR-sponsored activity are required to disclose to the planning committee and audience any financial or other relationships including, but not limited to:

None: Nothing to disclose1. Stock, stock options or bond holdings in a for-profit

corporation or self-directed pension plan2. Research grants3. Employment (full or part-time)4. Ownership or partnership5. Consulting fees or other remuneration (payment)6. Non-remunerative positions of influence such as officer,

board member, trustee or public spokesperson7. Receipt of royalties8. Speakers bureau9. Other

Speakers, moderators and abstract authors submitted their disclosure online prior to publication. Disclosures for invited speakers are listed in the indices by presenters last name.

Abstract author disclosures are published online and in a supplement to the October issue of Arthritis & Rheumatism. Disclosures for the Late-Breaking abstracts are published online and in the December issue of Arthritis & Rheumatism. Any individual who refuses to disclose relevant financial relationships will be disqualified from being a planning committee member, a presenter, an author of a CME activity, and cannot have control of, or responsibility for, the development, management, presentation or evaluation of the CME activity.

ACr DISCloSure PolICyIt is the policy of the American College of Rheumatology to ensure that its CME activities are independent and free of commercial bias.

To ensure content objectivity and balance, and guarantee that the content presented is in the best interest of its learners and the public, the ACR requires that everyone in a position to control content disclose all relevant financial relationships with any commercial interest if the relationship is financial and occurred within the past 12 months. If there are relationships that create a conflict of interest, these must be resolved in accordance with the ACRs CME Resolution of Conflict policy prior to the participation of the individual in the development or presentation of CME content.

CoPyrIGHt mAterIAlS PolICy The annual meeting is a private event. Programs presented at the meeting are for the education of attendees and purchasers of recorded presentations as authorized by the American College of Rheumatology. The information and materials displayed and presented during this meeting are the property of the ACR and the presenter and cannot be photographed, copied, photocopied, transformed to electronic format, reproduced, or distributed without written permission of the American College of Rheumatology and the presenter. Any use of the program content for commercial purposes, which includes, but is not limited to oral presentations, audiovisual materials used by speakers, and program handouts without the written consent of the ACR is prohibited. This policy applies before, during and after the meeting.

(See index for Authors Disclosures)

47.25

The ACR will enforce its intellectual property rights and penalize those who infringe upon it.

The names, insignias, logos and acronyms of the ACR, the ARHP and the REF are proprietary marks. Use of the names in any fashion, by any entity, for any purpose, is prohibited without the express written permission of the American College of Rheumatology.

emBArGo PolICy

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special supplement of Arthritis & Rheumatism. Information contained in those abstracts may not be released until the abstracts appear online. Academic institutions, private organizations and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract online.

However, the ACR continues to require that information that goes beyond that contained in the abstract, e.g., discussion of the abstract done as part a scientific presentation or presentation of additional new information that will be available at the time of the meeting, is under embargo until 5:00 pm Eastern Time on Saturday, November 5. Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate.

Authors are responsible for notifying financial and other sponsors about this policy.

SunDAy, novemBer 6, 2011

9:00 am - 6:00 pm ACR Poster Session APoster presenters will be available from 9:00 11:00 am.(Abstracts #1-717). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11:00 am - 12:30 pmACR Plenary Session IDiscovery 2011(Abstracts #718-722) . . . . . . . . . . . . . . . . . . . . . . . . . . . S279

2:30 - 4:00 pmACR Concurrent Abstract SessionsAntiphospholipid Syndrome(Abstracts #723-728). . . . . . . . . . . . . . . . . . . . . . . . . . . . S281

Cell-cell Interactions and Adhesion(Abstracts #729-734). . . . . . . . . . . . . . . . . . . . . . . . . . . . S284

Fibromyalgia and Soft Tissue Disorders I(Abstracts #735-740). . . . . . . . . . . . . . . . . . . . . . . . . . . . S286

Orthopedics and Low Back Pain(Abstracts #741-746). . . . . . . . . . . . . . . . . . . . . . . . . . . . S288

Pediatric Rheumatology - Clinical and Therapeutic Aspects: Clinical Characteristics(Abstracts #747-752). . . . . . . . . . . . . . . . . . . . . . . . . . . . S291

Quality Measures and Innovations in Practice Management and Care Delivery I(Abstracts #753-758). . . . . . . . . . . . . . . . . . . . . . . . . . . . S294

Rheumatoid Arthritis Clinical Aspects: Cardiovascular Disease(Abstracts #759-764). . . . . . . . . . . . . . . . . . . . . . . . . . . . S297

Rheumatoid Arthritis - Human Etiology and Pathogenesis I: Pathogenesis of the Earliest Stages of Rheumatoid Arthritis(Abstracts #765-770). . . . . . . . . . . . . . . . . . . . . . . . . . . . S300

Sjgrens Syndrome(Abstracts #771-776). . . . . . . . . . . . . . . . . . . . . . . . . . . . S302

Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment I(Abstracts #777-782). . . . . . . . . . . . . . . . . . . . . . . . . . . . S305

Systemic Lupus Erythematosus - Clinical Aspects: Cardiac Disease/Organ Damage(Abstracts #783-788). . . . . . . . . . . . . . . . . . . . . . . . . . . . S307

Vasculitis I(Abstracts #789-794). . . . . . . . . . . . . . . . . . . . . . . . . . . .

2:30 - 4:00 pmARHP Concurrent Abstract SessionARHP Epidemiology and Public Health I (Abstracts #795-800). . . . . . . . . . . . . . . . . . . . . . . . . . . .S313

4:30 - 6:00 pmACR Concurrent Abstract SessionsEpidemiology and Health Services Research V: Drugs(Abstracts #801-806). . . . . . . . . . . . . . . . . . . . . . . . . . . .S316

Imaging of Rheumatic Disease I: Ultrasonography and Dual-emission X-ray Absorptiometry (DEXA)(Abstracts #807-812). . . . . . . . . . . . . . . . . . . . . . . . . . . .S318

Innate Immunity and Rheumatic Disease(Abstracts #814-818). . . . . . . . . . . . . . . . . . . . . . . . . . . .S320

Muscle Biology, Myositis and Myopathies: Insights into the Pathogenesis of Myositis(Abstracts #819-824). . . . . . . . . . . . . . . . . . . . . . . . . . . . S322

Osteoarthritis - Clinical Aspects I(Abstracts #825-830). . . . . . . . . . . . . . . . . . . . . . . . . . . .S324

Rheumatoid Arthritis - Animal Models I(Abstracts #831-836). . . . . . . . . . . . . . . . . . . . . . . . . . . . S327

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Biomarkers(Abstracts #837-842). . . . . . . . . . . . . . . . . . . . . . . . . . . . S330

Systemic Sclerosis Fibrosing Syndromes and Raynauds - Clinical Aspects and Therapeutics I(Abstracts #843-848). . . . . . . . . . . . . . . . . . . . . . . . . . . . S332

T-cell Biology and Targets in Autoimmune Disease: Lymphocyte Biology and Targets in Autoimmune Disease(Abstracts #849-854). . . . . . . . . . . . . . . . . . . . . . . . . . . .S334

Vasculitis II(Abstracts #855-860). . . . . . . . . . . . . . . . . . . . . . . . . . . .S336

4:30 - 6:00 pmACR/ARHP Combined Abstract SessionACR/ARHP Combined Pediatrics Abstract Session(Abstracts #861-866). . . . . . . . . . . . . . . . . . . . . . . . . . . .S338

4:30 - 6:00 pmARHP Concurrent Abstract SessionARHP Clinical Practice/Patient Care I(Abstracts #867-872). . . . . . . . . . . . . . . . . . . . . . . . . . . .

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S1

S310S341

monDAy, novemBer 7, 2011

9:00 am - 6:00 pmACR/ARHP Poster Session B*(Abstracts in this session are not in sequential order. Abstracts #873 and #874 have been re-numbered as #2486A and #2486B and can be found on page 10).Poster presenters will be available from 9:00 11:00 am.(Abstracts #875-1586) . . . . . . . . . . . . . . . . . . . . . . . . . . S344

11:00 am - 12:30 pmACR Plenary Session IIDiscovery 2011(Abstracts #1587-1592). . . . . . . . . . . . . . . . . . . . . . . . . . S619

2:30 - 4:00 pmACR Concurrent Abstract SessionsEducation: Medical Education (Abstracts #1593-1598) . . . . . . . . . . . . . . . . . . . . . . . . . S622

Epidemiology and Health Services Research I: Gout (Abstracts #1599-1604). . . . . . . . . . . . . . . . . . . . . . . . . . S624

Fibromyalgia and Soft Tissue Disorders II(Abstracts #1605-1610). . . . . . . . . . . . . . . . . . . . . . . . . . S627

Imaging of Rheumatic Disease II: X-ray, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)(Abstracts #1611-1616) . . . . . . . . . . . . . . . . . . . . . . . . . . S629

Metabolic and Crystal Arthropathies I: Concurrent Session on Pathogenesis of Gout, a Potential Novel Therapy, and Validity of Dual Energy Computed Tomography(Abstracts #1617-1622). . . . . . . . . . . . . . . . . . . . . . . . . . S632

Osteoarthritis - Clinical Aspects II(Abstracts #1623-1628). . . . . . . . . . . . . . . . . . . . . . . . . . S634

Osteoporosis and Metabolic Bone Disease: Clinical Aspects and Pathogenesis(Abstracts #1629-1634). . . . . . . . . . . . . . . . . . . . . . . . . .S637

Rheumatoid Arthritis - Animal Models II(Abstracts #1635-1640). . . . . . . . . . . . . . . . . . . . . . . . . .S639

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Existing Biologics(Abstracts #1641-1646). . . . . . . . . . . . . . . . . . . . . . . . . . S641

Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment II(Abstracts #1647-1652). . . . . . . . . . . . . . . . . . . . . . . . . . S644

Systemic Lupus Erythematosus - Clinical Aspects: Renal(Abstracts #1653-1658). . . . . . . . . . . . . . . . . . . . . . . . . . S646

Systemic Lupus Erythematosus - Human Etiology and Pathogenesis I(Abstracts #1659-1664). . . . . . . . . . . . . . . . . . . . . . . . . .S649

2:30 - 4:00 pm ARHP Concurrent Abstract SessionARHP Education and Community Programs(Abstracts #1665-1670). . . . . . . . . . . . . . . . . . . . . . . . . .S651

4:30 - 6:00 pmACR Concurrent Abstract SessionsCytokines, Mediators, and Gene Regulation I(Abstracts #1671-1676). . . . . . . . . . . . . . . . . . . . . . . . . . S653

Genetics, Genomics, and Proteomics(Abstracts #1677-1682). . . . . . . . . . . . . . . . . . . . . . . . . . S656

Pediatric Rheumatology-Pathogenesis(Abstracts #1683-1688). . . . . . . . . . . . . . . . . . . . . . . . . . S658

Rheumatoid Arthritis Clinical Aspects: Clinical Features(Abstracts #1689-1694). . . . . . . . . . . . . . . . . . . . . . . . . .S661

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Existing Disease-modifying Antirheumatic Drugs (DMARDs) - Tight Control, Induction and Drug Withdrawal Trials(Abstracts #1695-1700). . . . . . . . . . . . . . . . . . . . . . . . . . S663

Spondylarthropathies and Psoriatic Arthritis Pathogenesis, Etiology(Abstracts #1701-1706). . . . . . . . . . . . . . . . . . . . . . . . . .S666

Systemic Lupus Erythematosus - Clinical Aspects: General(Abstracts #1707-1712). . . . . . . . . . . . . . . . . . . . . . . . . . S669

Systemic Sclerosis Fibrosing Syndromes and Raynauds - Clinical Aspects and Therapeutics II(Abstracts #1713-1718). . . . . . . . . . . . . . . . . . . . . . . . . . S672

4:30 - 6:00 pmACR/ARHP Combined Abstract SessionACR/ARHP Combined Rehabilitation Abstract Session(Abstracts #1719-1724). . . . . . . . . . . . . . . . . . . . . . . . . .S675

4:30 - 6:00 pmACR REF Special Session ACR REF Marshall J. Schiff, MD, Memorial Lectureship: Multicenter Orthopaedic Outcomes Network - A Prospective Longitudinal Cohort of Anterior Cruciate Ligament (ACL) Reconstruction Outcomes(Abstracts #1725-1726). . . . . . . . . . . . . . . . . . . . . . . . . .

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*Abstracts in this session are not in sequential order.

S677

4:30 - 6:00 pmARHP Concurrent Abstract Session ARHP Health Services Research(Abstracts #1727-1732). . . . . . . . . . . . . . . . . . . . . . . . . .S678

tueSDAy, novemBer 8, 2011

9:00 am - 6:00 pmACR Poster Session CPoster presenters will be available from 9:00 11:00 am.(Abstracts #1733-2426). . . . . . . . . . . . . . . . . . . . . . . . . .S681

11:00 am - 12:30 pmACR Plenary Session IIIDiscovery 2011(Abstracts #2427-2432). . . . . . . . . . . . . . . . . . . . . . . . . .S944

2:30 - 4:00 pmACR Concurrent Abstract SessionsBiology and Pathology of Bone and Joint: Molecular Targets for an Effective Therapy (Abstracts #2433-2438). . . . . . . . . . . . . . . . . . . . . . . . . .S947

Epidemiology and Health Services Research VI: Lupus/Vasculitis(Abstracts #2439-2444). . . . . . . . . . . . . . . . . . . . . . . . . .S949

Miscellaneous Rheumatic and Inflammatory Diseases(Abstracts #2445-2450). . . . . . . . . . . . . . . . . . . . . . . . . .S952

Pediatric Rheumatology - Clinical and Therapeutic Aspects: Predictors and Outcomes(Abstracts #2451-2456). . . . . . . . . . . . . . . . . . . . . . . . . . S954

Rheumatoid Arthritis Clinical Aspects: Diagnostic and Remission Criteria(Abstracts #2457-2462). . . . . . . . . . . . . . . . . . . . . . . . . .S957

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Existing Disease-modifying Antirheumatic Drugs (DMARDs) and Corticosteroids(Abstracts #2463-2468). . . . . . . . . . . . . . . . . . . . . . . . . . S960

Systemic Lupus Erythematosus - Clinical Aspects: New Therapies(Abstracts #2469-2474). . . . . . . . . . . . . . . . . . . . . . . . . . S962

Systemic Lupus Erythematosus - Human Etiology and Pathogenesis II: Genetics(Abstracts #2475-2480). . . . . . . . . . . . . . . . . . . . . . . . . . S965

Systemic Sclerosis Fibrosing Syndromes and Raynauds - Clinical Aspects and Therapeutics III(Abstracts #2481-2486). . . . . . . . . . . . . . . . . . . . . . . . . .S968

Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment(Abstracts #2486A-2486F) . . . . . . . . . . . . . . . . . . . . . . . S970

2:30 - 4:00* pmACR REF Special Session*(Abstracts in this session are not in sequential order. Abstracts #2487-2492 can be found directly below this session).REF Edmond L. Dubois, MD, Memorial Lectureship: Interfering with Vascular Health: How Innate Immunity Promotes Premature Organ Damage in Systemic Lupus Erythematosus (Abstracts #2547-2552) . . . . . . . . . . . . . . . . . . . . . . . . . .S997

2:30 - 4:00 pmARHP Concurrent Abstract SessionARHP Psychology/Social Sciences(Abstracts #2487-2492). . . . . . . . . . . . . . . . . . . . . . . . . .S973

4:30 - 6:00 pmACR Concurrent Abstract SessionsB-cell Biology and Targets in Autoimmune Disease(Abstracts #2493-2498). . . . . . . . . . . . . . . . . . . . . . . . . .S975

Cytokines, Mediators, and Gene Regulation II(Abstracts #2499-2504). . . . . . . . . . . . . . . . . . . . . . . . . . S977

Epidemiology and Health Services Research II: Osteoarthritis(Abstracts #2505-2510). . . . . . . . . . . . . . . . . . . . . . . . . . S980

Rheumatoid Arthritis Clinical Aspects: Predictors of Outcome(Abstracts #2511-2516) . . . . . . . . . . . . . . . . . . . . . . . . . .S982

Rheumatoid Arthritis - Human Etiology and Pathogenesis II: Pathogenesis of Rheumatoid Arthritis - Whats New?(Abstracts #2517-2522). . . . . . . . . . . . . . . . . . . . . . . . . . S985

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Further Insights into Efficacy and Safety of Tumor Necrosis Factor (TNF)-Inhibitors(Abstracts #2523-2528). . . . . . . . . . . . . . . . . . . . . . . . . .S987

Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment III(Abstracts #2529-2534). . . . . . . . . . . . . . . . . . . . . . . . . . S990

Systemic Sclerosis Fibrosing Syndromes and Raynauds - Pathogenesis, Animal Models and Genetics I(Abstracts #2535-2540). . . . . . . . . . . . . . . . . . . . . . . . . . S992

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*Abstracts in this session are not in sequential order.

4:30 - 6:00 pmARHP Concurrent Abstract Session*(Abstracts in this session are not in sequential order. Abstracts #2547-2552 can be found on page 10).ARHP Research Methodology(Abstracts #2553-2558). . . . . . . . . . . . . . . . . . . . . . . . . .S999

WeDneSDAy, novemBer 9, 2011

7:30 - 8:30 amARHP Concurrent Abstract SessionARHP Clinical Practice/Patient Care II(Abstracts #2561-2566). . . . . . . . . . . . . . . . . . . . . . . . . S1004

9:00 - 10:30 amACR Concurrent Abstract SessionsCytokines, Mediators, and Gene Regulation III(Abstracts #2567-2572). . . . . . . . . . . . . . . . . . . . . . . . . S1007

Epidemiology and Health Services Research III: Rheumatoid Arthritis(Abstracts #2573-2578). . . . . . . . . . . . . . . . . . . . . . . . . S1009

Metabolic and Crystal Arthropathies II: Anti-Gout Medications Dosing, Adverse Effects, and Economic Burden(Abstracts #2579-2584). . . . . . . . . . . . . . . . . . . . . . . . .S1012

Rheumatoid Arthritis Clinical Aspects: Risk of Cardiovascular Disease(Abstracts #2585-2590). . . . . . . . . . . . . . . . . . . . . . . . .S1014

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Novel Compounds I(Abstracts #2591-2596). . . . . . . . . . . . . . . . . . . . . . . . .S1017

Systemic Lupus Erythematosus - Clinical Aspects: Translational Studies(Abstracts #2597-2602). . . . . . . . . . . . . . . . . . . . . . . . .S1020

Systemic Sclerosis Fibrosing Syndromes and Raynauds - Pathogenesis, Animal Models and Genetics II(Abstracts #2603-2608). . . . . . . . . . . . . . . . . . . . . . . . .S1022

9:00 - 10:30 amARHP Concurrent Abstract Session*(Abstracts in this session are not in sequential order. Abstracts #2609-2614 can be found directly below this session).ARHP Clinical Practice/Patient Care III(Abstracts #2559A-2560) . . . . . . . . . . . . . . . . . . . . . . .

9:00 - 10:30 amARHP Concurrent Abstract SessionARHP Rehabilitation Science(Abstracts #2609-2614). . . . . . . . . . . . . . . . . . . . . . . . . S1025

11:00 am - 12:30 pmACR Concurrent Abstract SessionsInfection-Related Rheumatic Disease(Abstracts #2615-2620). . . . . . . . . . . . . . . . . . . . . . . . . S1027

Pediatric Rheumatology - Clinical and Therapeutic Aspects: Treatment(Abstracts #2621-2626). . . . . . . . . . . . . . . . . . . . . . . . . S1029

Rheumatoid Arthritis Treatment - Small Molecules, Biologics, Therapy: Novel Compounds II(Abstracts #2627-2632). . . . . . . . . . . . . . . . . . . . . . . . .S1032

Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment IV(Abstracts #2633-2638). . . . . . . . . . . . . . . . . . . . . . . . .S1035

11:00 am - 12:30 pmARHP Concurrent Abstract SessionARHP Epidemiology and Public Health II(Abstracts #2639-2644). . . . . . . . . . . . . . . . . . . . . . . . .

table of Contents

*Abstracts in this session are not in sequential order.

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. . . . . . . . . . . . . . . . . . . . . . . . .S1041ACR/ARHP Abstract

Author Disclosures . . . . . . . . . . . . . . . . . . . . . . . . .

ACR Poster Session AAntiphospholipid Syndrome

Sunday, November 6, 2011, 9:00 AM6:00 PM

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Lupus Anticoagulant at a High-Risk Clinic: Results From a 5-Year Reviewof 2,169 Patients. Christine A. Clark, Karen A. Spitzer and Carl A. Laskin. Uni-versity of Toronto and LifeQuest Centre for Reproductive Medicine, Toronto,ON

Background/Purpose: The lupus anticoagulant (LAC) Is one of severalantiphospholipid antibodies (aPL) that comprise laboratory criteria for theantiphospholipid syndrome (APS). From many studies of recurrent early preg-nancy loss (RPL) in the context of aPL, there is a perception that LAC is prevalentin this population. We wanted to determine the distribution of LAC positivity ata large tertiary clinic that sees about 250 new patients with RPL annually inaddition to those with SLE and/or APS. We also wanted to identify the mostfrequent clinical manifestations of APS associated with repeated LAC positivityand to establish any correlations with the number of positive LAC tests in a realworld setting.

Methods: We included all patients tested in our laboratory forLAC and anticardiolipin antibodies (aCL IgG and IgM) from 2005 to 2010.We reviewed charts of patients with repeated prolonged LAC to ascertaindiagnoses including histories of adverse obstetric and throm-botic events (TE). LAC were measured using a panel of 4 tests accord-ing not only to ISTH guidelines (DRVVT and PTT-LA) but also using dilutePT and KCT assays; aCL IgG and IgM were measured using INOVA kits.

Results: Over 5 years we measured 3,446 LAC for 2,169 patients (many hadmultiple tests). There were 370 (1.1%) positive LAC tests distributed among 138patients; 31 were positive on only one occasion of many retests, 43 were positivewith no subsequent tests, and 64 (3.2%) were positive on 2 occasions.Fifty-nine of 64 charts were available for review: 26 (44.1%) have APS; 19(32.2%) have SLE/APS; 7 (11.9%) have SLE and 7 (11.9%) have otherdiagnoses. Twenty-two patients (37.3%) have a history of TE, 7 (11.8%) havehad more than 1 TE; 13 patients (22.0%) have had a TE in the absence of apredisposing factor; 4 have had a post-partum TE (6.8%); 9 (15.2%) had a TEwhile on oral contraception. Twenty-four (40.7%) patients have had 1 stillbirth(SB); 9 (15.3%) have a history of IUGR; 6 (10.2%) had preeclampsia and/orHELLP during a pregnancy; and 3 (5.1%) have a history of early RPL only.Patients were evenly distributed among the number of positive tests in the 4-testLAC panel. There were no differences among distribution of SB, IUGR,preeclampsia or HELLP, early RPL, or live birth ever; however patients with 3 or4 positive in the LAC panel were significantly more likely to have had a TE thanthose with 1 or 2 positive (54.8% vs 21.4% respectively, p 0.017, 95% CI:0.0870.581). Neither mean values nor increased prevalence of 40 GPL orMPL aCL IgG or IgM were significantly different among the LAC positivegroups.

Conclusion: ISTH guidelines recommend using only 2-test LAC panel,but we found significantly more patients with TE were positive for 3compared to one or two of the LAC panel. A history of SB was the mostcommon clinical manifestation of repeatedly positive LAC, occurring twiceas frequently as idiopathic TE. LAC was found in 3% of patients attendinga tertiary clinic restricted to patients with SLE, APS and RPL, and in only0.2% of patients referred with a history of exclusively early RPL. Thesefindings reinforce the need to redefine APS and validate the proposition thatearly RPL should be excluded from the classification criteria.

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Effect of Normal Pregnancy on the Lupus Anticoagulant: No Need toEstablish Pregnancy-Specific Reference Ranges. Christine A. Clark, KarenA. Spitzer and Carl A. Laskin. University of Toronto and LifeQuest Centrefor Reproductive Medicine, Toronto, ON

Background/Purpose: The physiological basis for the hypercoagulability ofpregnancy is well understood. Shortened clotting times, especially later inpregnancy, may be a result of increased Factor VIII and fibrinogen levels.Whether alterations in these coagulation and hemostatic mechanisms also result ina change in the normal ranges for the lupus anticoagulant (LAC) remainscontroversial. Some investigators have reported data indicating no change duringpregnancy (Derksen et al, 1992) and yet recent ISTH guidelines suggest thatspecific pregnancy-related reference ranges be used when measuring the LACduring pregnancy (J Thromb Hemost 2009;7:173740). We wanted to determineif the LAC varies in healthy women between ante- and post-partum plasmasamples.

Methods: We recruited 53 consecutive healthy pregnant women with nohistory of obstetric, hematologic, or autoimmune abnormalities as part of anongoing study (PROMISSE). Non-study plasma samples were collected duringpregnancy and post-partum and were analysed for the presence of LAC using apanel of 4 tests including dilute Russells viper venom time (dRVVT), diluteprothrombin time (DPT), a lupus-anticoagulant sensitive PTT (PTT-LA), andkaolin clotting time (KCT). We compared values from samples collected between2027 weeks gestation and again post partum and determined not only if therewas a statistical difference between the 2 groups, but also if the values wereoutside previously established reference ranges from a general population sample.

Results: There was no significant difference between ante- and post-partumPTT-LA [median (range) 38.0 (29.056.5) vs. 39.7 (31.269.0 sec) respectively,p 0.27], dRVVT [32.7 (23.350.0) vs. 30.8 (20.339.1); p 0.07), or KCT[55.5 (35.090.7) vs. 54.4 (33.5104.2); p 0.81]. Results for dPT showed asignificant decrease during pregnancy [39.0 (22.954.1)] compared to post-partum [44.1 (24.5 65.0); p 0.001, (95% CI for the difference of means:4.410.4)]. However, this pregnancy-related difference did not fall outside thenon-pregnant reference range for dPT in our laboratory.

Conclusion: Normal pregnancy did not affect the dRVVT, PTT-LA orKCT. Only the dPT showed a pregnancy-related decrease, but although thedifference between mean pregnant and non-pregnant clotting times wasstatistically significant, both pregnant and non-pregnant ranges were withinthe general population reference range for this assay. Our results supportDerksens earlier findings and we conclude that any changes in LAC levels innormal pregnancy, if present at all, are too small to necessitate the use ofpregnancy-specific reference ranges, as suggested in the ISTH guidelines.

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Association of IgG, IgM, and IgA Isotypes of Anticardiolipin Alone or InCombination In Prediction of Thrombosis In Systemic Lupus Erythem-atosus. Vinicius Domingues, Hong Fang and Michelle Petri, Johns Hopkins.University School of Medicine, Baltimore, MD

Background/Purpose: The Sydney APS Classification Criteria includemedium to high titer anticardiolipin IgG or IgM. We explored the association ofall anticardiolipin isotypes, singly or in combination, with thrombosis in SLE.

Methods: There were 1567 SLE patients (92% female, 55% Caucasian,37% African-American, mean age at entry 39.612.9) who participated.There were 668 total thrombotic events (arteral: total 328, TIA 67, stroke 129,myocardial infarction 58, digital gangrene 31, other arterial 45; venous: total340, DVT or PE 211, superficial 54, other venous 75). Anticardiolipin IgG,IgM, or IgA were assessed at each visit (Inova Diagnostics Inc, San Diego,CA), with cut-offs of 20 for medium positive and 40 for high positive.

Results:Assay OR P-value

Venous ThrombosisIgG 20 ever pos 2.26 (1.70,3.00) 0.0001IgG 40 ever pos 2.34 (1.65,3.34) 0.0001IgM 20 ever pos 1.32 (0.98,1.78) 0.0688IgM 40 ever pos 1.46 (1.01,2.11) 0.0432IgA 20 ever pos 2.17 (1.42,3.31) 0.0006IgA 40 ever pos 2.14 (1.18,3.87) 0.0176IgG 20 OR IgM 20 ever pos 1.79 (1.38,2.32) 0.0001IgG 40 OR IgM 40 ever pos 1.81 (1.34,2.45) 0.0002IgG 20 OR IgA 20 ever pos 2.06 (1.56,2.71) 0.0001IgG 40 OR IgA 40 ever pos 2.03 (1.44,2.87) 0.0001Arterial ThrombosisIgG 20 ever pos 1.95 (1.45,2.620 0.0001IgG 40 ever pos 2.39 (1.67,3.43) 0.0001IgM 20 ever pos 1.42 (1.05,1.93) 0.0264IgM 40 ever pos 1.68 (1.16,2.44) 0.0081IgA 20 ever pos 1.99 (1.28,3.09) 0.0036IgA 40 ever pos 2.75 (1.55,4.98) 0.0013IgG 20 OR IgM 20 ever pos 1.70 (1.30,2.23) 0.0002IgG 40 OR IgM 40 ever pos 1.96 (1.44,2.67) 0.0001IgG 20 OR IgA 20 ever pos 1.79 (1.34,2.39) 0.0001IgG 40 OR IgA 40 ever pos 2.49 (1.77,3.52) 0.0001StrokeIgG 20 ever pos 1.74 (1.17,2.60) 0.0087IgG 40 ever pos 2.19 (1.37,3.51) 0.0025IgM 20 ever pos 1.34 (0.89,2.03) 0.1787IgM 40 ever pos 1.25 (0.74,2.11) 0.3910IgA 20 ever pos 1.54 (0.84,2.84) 0.1528IgA 40 ever pos 2.02 (0.93,4.37) 0.772IgG 20 OR IgM 20 ever pos 1.53 (1.06,2.21) 0.0242IgG 40 OR IgM 40 ever pos 1.70 (1.12,2.58) 0.0506IgG 20 OR IgA 20 ever pos 1.51(1.02,2.24) 0.0506IgG 40 OR IgA 40 ever pos 2.00 (1.26,3.17) 0.0045

Conclusion: Analysis of single isotypes found that IgG or IgA, 20 or 40 (but not IgM) were associated with venous thrombosis. For arterialthrombosis, all single isotypes were associated. For stroke, only IgG was

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associated. Combinations of isotypes surprisingly did not add to the strengthof the association nor to the statistical significance. We conclude that: 1) theassociation depends on whether it is venous thrombosis, arterial thrombosis,or stroke (which is important predictive information for clinicians); 2) IgAanticardiolipin should be added to the classification criteria for APS in SLE,as it performs better than IgM; and 3) combining different isotypes ofanticardiolipin does not improve the association.

4

Anti-beta2 Glycoprotein I IgA in Systemic Lupus Erythematosus VersusControls. Ana-Maria Orbai1, Hong Fang1, Joan T. Merrill2, Graciela S.Alarcon3, Caroline Gordon4, Paul R. Fortin5, Ian N. Bruce6, David A.Isenberg7, Daniel J. Wallace8, Ola Nived9, Gunnar K. Sturfelt10, RosalindRamsey-Goldman11, Sang-Cheol Bae12, John G. Hanly13, Jorge Sanchez-Guerrero14, Ann E. Clarke15, Cynthia Aranow16, Susan Manzi17, Murray B.Urowitz18, Dafna D. Gladman19, Kenneth C. Kalunian20, Melissa I. Cost-ner21, Laurence S. Magder22, Systemic Lupus International CollaboratingClinics (SLICC)23 and Michelle Petri1. 1Johns Hopkins University School ofMedicine, Baltimore, MD, 2Oklahoma Medical Research Foundation, Okla-homa City, OK, 3University of Alabama at Birmingham, Birmingham, AL,4University of Birmingham, Birmingham, United Kingdom, 5Toronto West-ern Hospital, Toronto, ON, 6A, Manchester, United Kingdom, 7UniversityCollege London, London WC1E 6JF, United Kingdom, 8Cedars-Sinai/UCLA, Los Angeles, CA, 9University Hospital, Lund, Sweden, 10UniversityHospital Lund, Lund, Sweden, 11Northwestern University Feinberg School ofMedicine, Chicago, IL, 12Hanyang University Hospital for Rheumatic Dis-eases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul,South Korea, 13Dalhousie University, Halifax, NS, 14University HealthNetwork/Mount Sinai Hospital, Toronto, ON, 15Research Institute of theMcGill Univ. Health, Montreal, QC, 16Feinstein Institute for Medical Re-search, Manhasset, NY, 17Allegheny Singer Research Institute, Pittsburgh,PA, 18Toronto Western Hospital and University of Toronto, Toronto, ON,19Toronto Western Research Institute, University of Toronto, UniversityHealth Network, Toronto, ON, 20UCSD School of Medicine, La Jolla, CA,21North Dallas Dermatology Assoc, Dallas, TX, 22University of Maryland,Baltimore, MD, 23Chicago

Background/Purpose: Anti-beta2 glycoprotein I (GPI) is not part of theACR classification criteria for SLE, and IgA isotypes are omitted from theclassification criteria for APS. We studied the prevalence and associations ofanti-beta2 glycoprotein I IgA in a large multi-center study.

Methods: The dataset consisted of 1384 patients with both anti-beta2-GPIIgA measured and a consensus physicians diagnosis (657 with SLE and 727controls with other rheumatologic diseases). Of the 657 SLE patients, 599(91%) were female, 394 (60%) were Caucasian, 134 (20%) were of Africandescent, and 76 (12%) were Asian. Their mean age (years) was 37.913.3.P-values were calculated based on the chi-square test (SAS Institute, Cary,NC, USA).

Results: The prevalence of anti-beta2-GPI IgA was 14% (94/657) in SLEpatients and 7% (49/727) in controls (P-value0.0001, OR2.3 (95% CI:1.6, 3.3)). Eleven percent (73/657) of SLE patients had anti-beta2-GPI IgAalone (no anti-beta2-GPI IgG or IgM).

Table 1. Percentage of SLE Patients with Anti-beta2-GPI IgA, by DemographicVariables

Percentage withAnti-beta2-GPI IgA P-value

Ethnicity African Descent 21.6 0.019Caucasian 11.4Asian 18.4Other 11.3

Gender Female 14.2 0.78Male 15.5

Age 30 20.3 0.003530 11.7

Table 2. Percentage of SLE Patients with Various Clinical Conditions, byAnti-beta2-GPI IgA Status

ACR criteriaAnti-beta2-GPI

IgA (%)

NoAnti-beta2-GPI

IgA (%) P-valueOdds Ratio(95% CI)

Adjusted P-valuefor Race and

Age

Malar Rash 52.1 43.5 0.12 1.4 (0.9, 2.2) 0.16Discoid Rash 20.2 17.9 0.60 1.3 (0.7, 2.2) 0.42Photosensitivity 48.9 51.0 0.71 1.0 (0.6, 1.5) 0.91Oral Ulcers 38.3 41.6 0.55 0.9 (0.6, 1.4) 0.57

Arthritis 66.0 65.9 0.99 1.0 (0.6, 1.6) 0.93Serositis 38.3 30.9 0.15 1.3 (0.8, 2.0) 0.33Pleurisy 34.0 25.4 0.08 1.4 (0.9, 2.3) 0.16Pericarditis 12.8 10.8 0.58 0.9 (0.5, 1.9) 0.86Renal 39.4 31.1 0.11 1.1 (0.7, 1.8) 0.63Proteinuria 37.2 30.0 0.16 1.1 (0.7, 1.8) 0.71Urinary casts 9.6 7.1 0.40 1.1 (0.5, 2.5) 0.73Neurologic 6.4 7.1 0.80 0.8 (0.3, 2.1) 0.72Seizure 5.3 5.5 0.94 1.0 (0.4, 2.6) 0.92Psychosis 3.2 2.0 0.44 1.5 (0.4, 5.8) 0.54Hematologic lupus 61.7 49.7 0.032 1.5 (0.9, 2.4) 0.09Leukopenia 35.1 28.4 0.19 1.2 (0.7, 1.9) 0.56Lymphopenia 29.8 30.9 0.83 0.9 (0.6, 1.5) 0.72Thrombocytopenia 18.1 14.0 0.30 1.2 (0.7, 2.3) 0.46Anti-dsDNA 75.5 57.0 0.0007 2.4 (1.4, 4.1) 0.001Anti-Smith 25.5 23.6 0.69 0.8 (0.5, 1.4) 0.51Lupus anticoagulant 70.2 48.9 0.0001 2.4 (1.5, 3.9) 0.0003Anticardiolipin IgG 40.4 16.2 .0001 3.0 (1.9, 5.0) .0001Anticardiolipin IgM 35.1 11.6 .0001 4.0 (2.4, 6.7) .0001Anticardiolipin IgA 8.5 0.9 .0001 10.8 (3.2, 36.8) 0.0001False positive RPR 9.6 3.4 0.032 3.3 (1.1, 10.1) 0.033

Table 3. Sensitivity and Specificity for SLE, based on Anti-beta2 Glycoprotein IIgA Positivity

Sensitivity % Specificity %

Anti-beta2-GPI IgA 14.3 93.3

Conclusion: Anti-beta2 glycoprotein I IgA was more prevalent in SLEpatients (14%) than in patients with other rheumatologic diseases (7%) in thisinternational multi-center study. It can occur as the sole isotype of anti-beta2-GPI in SLE. It was strongly associated with age, anti-dsDNA and otherantiphospholipid antibodies and was highly specific for SLE. This was therationale to include anti-beta2 glycoprotein I IgA in the new SLICCclassification criteria for SLE.

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Risk Factors for Rethrombosis In Patients with Primary Antiphospho-lipid Syndrome Regardless of Their Oral Anticoagulation Status. Gabri-ela Hernandez-Molina1, Grissel Espericueta-Arriola2 and Antonio R. Cabral3.1Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran,Mexico City, Mexico, 2Instituto Nacional de Ciencias Medicas y NutricionSalvador Zubiran, Mexico city, Mexico, 3Instituto Nacional de CienciasMedicas y Nutricion Salvador Zubiran, Mexico, Mexico

Background/Purpose: To ascertain the serological and non-serologicalfactors for rethrombosis in patients with primary antiphospholipid syndrome(PAPS) regardless of their anticoagulation status.

Methods: We retrospectively studied patients with PAPS who had at leastone thrombotic episode. Patients were excluded if they had a history ofhereditary thrombophilia or SLE. We divided patients in 4 groups. 1: Patientson oral anticoagulants (OA) that after discontinuation (self decision ormedical contraindication) developed a new thrombotic event. 2: Patients onOA that after discontinuation did not have a new thrombotic event. 3: Patientson continuous OA that have remained thrombosis-free. 4: Patients on OAwho developed a new thrombotic event. We studied: age at time ofthrombosis, time for rethrombosis, BMI, comorbidities (DM2, hypertension,dyslipidemia), pregnancies, bedridden, hormonal contraception, estrogenreplacement, perioperative period, infections, tobacco use, prednisone, aspi-rin, immunosuppresors and INR during thrombosis. We also evaluated thefrequency of aCL (IgG-IgM), anti-2GP-I (IgG-IgM), lupus anticoagulant(alone or combined) and persistently positive antibody titers. We usedANOVA, X2, Students t test and Odds Ratio (95% CI).

Results: We studied 95 patients (70 women, 74%): 32 (group 1), 25(group 2), 29 (group 3) and 10 (group 4). Their overall mean age at time ofstudy was 41.7 14 years with a median follow-up of 4.5 years (0.326).Follow-up time was shorter for group 1 (2.8 years, p 0.05) than the othergroups. LA and triple markers (LA, aCL and anti-2GP-I ) were moreprevalent in group 1 than in group 2: 67 vs. 31%; OR 4.5; 95% CI1.314.9; p 0.01; and 57% vs. 27%; OR 6.6; 1.725.2; p0.03 respec-tively. These two variables remained associated with recurrence of thrombo-sis after comparing groups 1 & 4 with group 2: LA 62% vs. 31%, OR 3.6;95% CI 1.111.2, p0.03; triple marker 75% vs. 27%; OR 8.0; 95% CI2.1429.8; p 0.04. Patients from group 2 were more frequently on aspirinthan those from group 3 (62.4% vs. 31%; OR 0.27; 95% CI 0.080.84;p0.02). We found no significant difference between the INR of our patientson oral anticoagulants (Group 3, INR 2.7 vs. group 4 2.3, p0.2). Neithertiters nor persistently positive antibody markers were associated with re-

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thrombosis. Other studied clinical variables were not associated with recurrentthrombosis.

Conclusion: Our study showed that LA, alone or combined with aCL andanti-2GP-I, is a risk factor for recurrent thrombosis in patients with PAPSregardless of therapeutically effective oral anticoagulation.

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Risk of Recurrent Stroke in Pregnancies of Patients with Antiphospho-lipid Syndrome and Previous Cerebral Ischemia. Rebecca Fischer-Betz,Christof Specker and Matthias Schneider. MNR-Klinik, Dusseldorf, Ger-many

Background/Purpose: Cerebral ischemia is one of the most prominentclinical manifestations of Antiphospholipid Syndrome (APS) and may bepresent with transient ischemic attacks (TIA) or stroke. There are only raredata on maternal and fetal outcome in pregnancies in women with previouscerebral ischemia.

Methods: We prospectively studied the outcome of 21 pregnancies inwomen with APS (10 primary and 11 secondary to SLE) and previouscerebral ischemia. 12 patients had previous transient ischemic attacks (TIAs)and 9 had stroke before pregnancy. The mean age at pregnancy was 30.5years ( 5.08). The time between cerebral ischemia and pregnancy rangedfrom 14182 months (median 70 months). All patients received treatmentwith aspirin 100 mg daily. 17 patients received low molecular weight heparin(LMWH). 4 patients were treated with warfarin before pregnancy andswitched to therapeutic doses of LMWH.

Results: There were 18 live births (85.7 %) and 3 (14.3 %) pregnancylosses (1 at 10 weeks, 1 at 22 and 1 at 24 weeks). All together, 7/21 (33.3 %)women developed preeclampsia. 12/18 (66.6 %) deliveries were preterm(mean weeks of gestation 36.1 2.27). 88.2 % underwent ceasarean section.The mean birth weight of the life born children was 2871 ( 563) g. Onefemale child was born with a nasal hypoplasia. 1 patient who switched fromwarfarin to heparin presented with TIA during her 34th week of pregnancy,despite this, she had a normal pregnancy. 1 pregnancy was complicated by afurther cerebral ischemic event at 3 weeks postpartum in a patient whounintentionally discontinued her aspirin medication while she was breastfeeding. 1 woman developed a third ischemic event 1 year post partum despitecontinuous treatment.

Conclusion: Our data suggest that successful pregnancy and delivery ispossible in APS patients with a history of cerebral ischemia. Despite thetreatment with low-dose aspirin and anticoagulants there is a high risk forpreterm deliveries and preeclampsia, but the risk for a recurrent cerebral eventseems to be low. A previous episode of cerebral ischemia therefore may notbe an absolute contraindication for an APS patient to become pregnant.

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Utility of the Systemic Lupus International Collaborating Clinics(SLICC)/American College of Rheumatology (ACR) Damage Index forAntiphospholipid Antibody (aPL) Positive Patients. Medha Barbhaiya1,Doruk Erkan2, Esther Rodriguez-Almaraz3, Glendalee Ramon4, JoAnn Vega4

and Michael D. Lockshin4. 1Weill Cornell Medical Center, New York, NY,2Barbara Volcker Center for Women and Rheumatic Diseases, Hospital forSpecial Surgery, New York, NY, 3Hospital 12 de Octubre, Madrid, Spain,4Barbara Volcker Center for Women and Rheumatic Diseases: Hospital forSpecial Surgery, New York, NY

Background/Purpose: SLICC/ACR Damage Index (DI) was designedand validated for systemic lupus erythematosus (SLE) patients to capturenon-reversible organ damage, not related to active inflammation, lasting atleast 6 months. Although aPL-positive patients with or without SLE developaPL-related organ damage, no DI exists specific for these patients. Thepurpose of this pilot study was to assess the utility of SLICC/ACR DI inaPL-positive patients.

Methods: We identified two groups of persistently aPL-positive patients(positive LA test, aCL IgG/M/A 20U, and/or a2GPI IgG/M/A 20U atleast 12 weeks apart) from our aPL-registry: those without other systemicautoimmune diseases (SAIDx) and those only with SLE. All patients areassessed by SLICC/ACR DI and ACR SLE Classification Criteria (CC) atthe registry entry. For the purpose of this study, we descriptively analyzedthe limitations of SLICC/ACR DI use in aPL-positive patients. We groupedpatients as (A) aPL only (no history of thrombosis, no SLE), (B) aPLwith SLE-like Disease (ACR_SLE_CC3/11), (C) aPL with SLE(ACR_SLE_CC3/11), (D) APS (history of thrombosis, no SLE); (E) APSwith SLE-like Disease, and (F) APS with SLE. We used One-Way ANOVA

test with Games-Howell post hoc analysis to compare the mean SLICC/ACRDI scores between six groups.

Results: Of 51 patients (mean age at the time of the registry entry 39.5 13.6), 73% were female and 86% were Caucasian. Top two limitations ofSLICC/ACR DI use in aPL-positive patients were: a) not being able to recordaPL-related damage (livedo reticularis/racemosa, adrenal infarcts requiringchronic treatment, diffuse pulmonary hemorrhage resulting in chronic symp-toms, permanent inferior vena cava filter placement, multiple sclerosis-likedisease, and/or white matter changes); and b) the definition of the twoSLICC/ACR DI items (venous thrombosis with swelling, ulceration, ORvenous stasis for at least 6 months; skin ulceration [excluding thrombosis]for more than 6 months). For the purpose of further analysis we created anexperimental category for aPL-related damage assigning the above damageitems one point each. We also scored all venous events and skin ulcers as onepoint. Table shows mean disease duration since the first positive aPLdetermination and SLICC/ACR DI using the original as well as the experi-mental criteria.

Patient Groups (n)**Mean DiseaseDuration (y)

Mean SLICC/ACRDamage Index

Score (Original)*

Mean SLICC/ACRDamage Index Score

(Experimental)*

A. aPL with no SLE (7) 5.72 8.00 1.29 0.95 2.00 1.16B. aPL with SLE-like (5) 2.15 2.18 1.80 1.64 2.20 2.38C. aPL with SLE (4) 1.50 0.82 1.00 0.00 1.75 0.96D. APS with no SLE (19) 2.60 2.81 2.32 1.30 2.79 1.55E. APS with SLE-like (8) 5.57 5.99 2.88 2.41 3.13 2.70F. APS with SLE (8) 5.65 3.50 5.50 2.44 6.50 2.93

* p0.0005, One-Way ANOVA. ** p0.05: A vs F, C vs D, C vs F for the original, and A vs F, C vs F,for the experimental SLICC/ACR DI

Conclusion: In persistently aPL-positive patients, the SLICC/ACR Dam-age Index: a) captures most, but not all, of aPL-related organ damage; and b)increases with additional aPL- and/or lupus-related damage. In persistentlyaPL-positive SLE patients, the SLICC/ACR Damage Index should beinterpreted cautiously as it can overestimate lupus-related, and underestimateaPL-related damage. Our study provides a start point to modify and validatethe SLICC/ACR Damage Index for aPL-positive patients.

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Development and Initial Validation of a Chronic Damage Index inPatients with Antiphospholipid Syndrome. Mary-Carmen Amigo1, LeonorA. Barile2, Alberto Barragan3, Gisela Espinosa-Cuervo4, Mavis Goycochea5,Laura Aline Martinez-Martinez6, Gabriela Medina7, Angelica Vargas8 andLuis J. Jara-Quezada9. 1ABC Medical Ctr, Mexico City, Mexico, 2HospitalEspecialidades CMN, Mexico City, Mexico, 3Mexico, Mexico, 4ResearchUnit, Mexican College of Rheumatology, Mexico, Mexico, 5Instituto Mexi-cano del Seguro Social and Research Unit, Mexican College of Rheumatol-ogy, Mexico City, Mexico, 6Intituto Nacional de Cardiologia, Mexico,Mexico, 7Seris/Zachila s/n La Raza, Mexico City, Mexico, 8Instituto Nac deCardiologia, Mexico City, Mexico, 9Hospital de Especialidades CentroMedico La Raza, IMSS, Mexico City, Mexico

Background/Purpose: The antiphospholipid syndrome (APS) is definedby the presence of venous or arterial thrombosis or recurrent pregnancycomplications in association with antiphospholipid antibodies. Certain keymanifestations are associated with a worse prognosis and permanent organdamage; but, at this time, there is not a comprehensive assessment ofaccumulative damage APS

Purpose: To describe the development and initial content, criterion andconstruct validity of a disease specific cumulative Damage Index in APS(DIAPS)

Methods: Phase 1 included generation for index content through anexpert panel agreement, a list of items considered to reflect the damage inAPS was generated in three rounds. An initial list of 60 manifestations linkedwith potential irreversible damage were identified by experts, then by anoperative definition to report each manifestations was established; finallyafter independent revision by 3 clinicians experts in methodology and 3 APSexperts a consensus round selected 47 items. A second phase was across-sectional study conducted in patients with APS diagnosis included in amulticentre electronic registry http://investigacion.colmexreuma.org.mx/saaf/index.html. The output rating was determined by the physician if eachmanifestation was absent (0), present but without sequel (1), or present withsequel (2). The final score was made adding the output rating reflecting thedamage for domains and global index. Quality of life related to health statuswas evaluated with Euroqol for construct validation, considering that thisanalysis could reflect a good agreement among the physicians on the

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assessment damage in the patients; Cronbach and correlation with Euroqolscale were calculated with SPSS 18.0, (p0.05)

Results: DIAPS was evaluated in 139 cases, female 76.4% (113), themean of the age at diagnosis 35.5 12.4 years; primary APS diagnosis in72.6% (119), APS plus SLE in 22% (36) and APS plus Sjogren in 1.8% (3).The most common comorbidities were obesity 24.3% (36), depression 18.2%(27) and dyslipidemia 14.2% (21). The most frequent manifestations condi-tioning sequels were: deep venous thrombosis 26.6% (37) and ischemicstroke 11.5% (16). Blindness 5.8% (8); retinal occlusive vessel disease 4.3%(6); myocardial infarction 2.9% (4); Cardiac valve requiring replacement1.4% (2); sequel of mesenteric thrombosis (including liver, spleen andintestine) 3.6% (5) and renal insufficiency 1.4% (2); The index has a highhomogeneity ( Cronbach 0.954). Questionnaire DIAPS showed correlationwith Euroqol as follow: pain (r 0.479, p 0.000), mobility (r 0.425, p 0.000),personal care (r 0.344, p 0.000), daily activities (r 0.329, p 0.000), currenthealth status (r 0.249, p 0.003) and anxiety/depression (r 0.192, p 0.025).

Conclusion: The preliminary validation study demonstrated content,criterion and construct validity of a new physician-reported instrument ofAPS damage. DIAPS has a good correlation with Euroqol. Further studieshave to be conducted to examine reliability and psychometric properties inextended populations. DIAPS could be a useful clinical tool and a goodinstrument in epidemiological and economic evaluations to measure the realimpact of this severe disease.

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Low Vitamin D Levels Are Common in Primary AntiphospholipidSyndrome: A Role in the Pathogenesis of the Disease? Laura Andreoli1,Silvia Piantoni1, Flavio Allegri1, Pier Luigi Meroni2 and Angela Tincani1.1Rheumatology Unit, University of Brescia, Brescia, Italy, 2University ofMilan, Milan, Italy

Background/Purpose: Low levels of vitamin D (vit.D) have beendescribed in different systemic autoimmune diseases (SAD). In vitro studiesand animal models have shown anti-inflammatory properties of vit.D.Therefore, hypovitaminosis D has been claimed to be involved in thepathogenesis of SAD. Primary Antiphospholipid Syndrome (PAPS) is char-acterized by thrombotic events and/or obstetric disease, whose pathogenesis ismediated by antiphospholipid antibodies. Differently from other SAD, PAPSpatients (pts) do not usually have a full-blown disease that requires cortico-steroids (and therefore the association of vit.D supplementation as osteo-porosis prophylaxis), nor have particular limitations in sun exposure. Thesefactors are relevant to vit.D levels. Thus, pts with PAPS appear to be a goodmodel for studying hypovitaminosis D in SAD. Purpose:To assess theprevalence of hypovitaminosis D in a large cohort of PAPS (in comparisonwith normal population from the same geographical area) and investigate theassociation with clinical manifestations.

Methods: We enrolled 115 PAPS (19 m, 96 f, median age: 46 years) and128 normal healthy donors (NHD) (55 m, 73 f, median age: 34). Vit.D levelswere tested by the LIAISON chemiluminescent immunoassay (DiaSorin,Italy), kindly provided by the manufacturer. The samples were grouped uponthe season for statistical analysis.

Results: Vit.D deficiency (10 ng/ml) was more prevalent in PAPS thanNHD (17% vs. 5%). Seasonal variability was present in both groups (higherlevels in the summer, lower levels during winter). However, median valueswere lower in PAPS than NHD at all time points, with the greatest differenceduring summertime (median: 28 vs. 40.1 ng/ml; p0.01), suggesting thatPAPS pts may be somehow prevented from vit.D generation upon sunexposure. PAPS pts may receive specific instructions regarding the use ofsunscreens in the presence of positive anti-nuclear antibodies (ANA). Com-paring pts with positive (n63) and negative ANA (n40), we foundcomparable Vit.D levels during the summer (median: 27.7 vs. 28). PAPSwere subdivided upon clinical features (thrombotic vs obstetric). Both groupshad lower vit.D levels than NHD. Thrombotic PAPS had significantly lowerlevels than obstetric PAPS (median value: 20.8 vs. 33.3; p0.01).

Conclusion: Pts with PAPS displayed significantly lower levels of vit.Dthan NHD. Although these pts have limited inflammatory burden and organinvolvement, rarely requiring immunosuppression, these epidemiological datamake them similar to pts with SAD such as Systemic Lupus Erythematosusor Rheumatoid Arthritis. Using ANA positivity as a surrogate marker for sunexposure, we suggest that sun avoidance may not be the main reason for lowvit.D levels. Hypovitaminosis D may be part of the mosaic of factors thatdetermine autoimmunity, rather than a consequence of chronic disease and itstreatment (factors that are poorly represented in PAPS). In particular, thishypothesis may be supported by the observation that pts with thromboticPAPS, i.e. more aggressive disease, are more deficient than those with

exclusive obstetric manifestations. This could fit well with a recent in vitroobservation of anti-thrombotic properties of vit.D.

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Thrombin Generation Indicates An Increased Risk for ThromboembolicEvents in Lupus and Antiphospholipid Patients. A Prospective CohortStudy. Stephane Zuily1, Veronique Regnault2, Francis Guillemin3, PierreKaminsky4, Thomas Lecompte5 and Denis Wahl6. 1Vascular Medicine Unit,Vandoeuvre-Les-Nancy, France, 2INSERM U961, Vandoeuvre, France,3Faculte de Medecin/BP 184, Vandoeuvre-les-Nancy, France, 4Orphan dis-ease Unit, Vandoeuvre, France, 5Haematology, Vandoeuvre, 6Nancy Univer-sity Hospital and INSERM U961, Vandoeuvre-Les-Nancy, France

Background/Purpose: Predicting thrombosis in systemic lupus erythem-atosus (SLE) and/or antiphospholipid antibodies (aPL)-positive patients is anunsolved issue. Our objective was to perform a prospective cohort study todetermine clinical and laboratory risk factors for thrombotic events includinga novel thrombin generation (TG)-based activated protein C (APC) resistanceassay in this population.

Methods: Ninety-two patients with SLE (n30) and/or aPL (n77)without anticoagulant treatment at inclusion were studied. Time to thromboticevent was determined according to clinical and laboratory variables (inheritedthrombophilia, aPL profiles) and APCsr-aPL (TG-based APC sensitivityratio: APCsr 90th percentile of values from a control population, andpersisting aPL positivity).

Results: Ninety two patients (74 women) (median age 40 years [inter-quartile range IQR: 2958]) were followed-up during a median duration of 35months (IQR: 2662; 320 patient-years). Thrombosis during follow-upoccurred in 18 patients: 4 arterial, 11 venous including 7 superficial venousthrombosis (SVT), 3 small vessel thromboses. In survival analyses, thepresence of APCsr-aPL was associated with an increased risk of thromboticevents during follow-up (HR, 3.67 [95%CI, 1.3110.31]) while the riskassociated with patients positive for all aPL tests (triple positive) was notsignificant (HR, 2.32 [95%CI, 0.767.13]).

Conclusion: APC-resistance determined by thrombin generation predictsthe risk for thromoembolic events in patients with antiphospholipid anti-bodies.

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Myocardial Global Longitudinal Strain in Primary AntiphospholipidSyndrome. Gabriela Medina, Eduardo Gomez-Banuelos, Erick Calderon-Aranda and Luis J. Jara. Hospital de Especialidades Centro Medico La Raza,IMSS, Mexico City, Mexico

Background/Purpose: Measurement of myocardial deformation orGlobal longitudinal strain (GLS) by speckle tracking echocardiography (STE)is useful for detection of microvascular damage and myocardial contractilityimpairment in patients with diabetes mellitus and ischemic cardiopathy.Primary antiphospholipid syndrome (PAPS) is characterized by thrombosis,endothelial damage, and vascular dysfunction. GLS has not been studied inthese patients.

Purpose: To evaluate the GLS from the left ventricle by STE in order toprovide the early detection of myocardial dysfunction in patients with PAPS.

Methods: Patients with PAPS older than 16 years of age, without signsand symptoms of heart failure and angina were recruited and matched withhealthy controls by age and gender. Patients with uncontrolled thyroiddisease, poor echocardiographic window, or pregnancy were excluded.Demographic, clinical data, cardiovascular risk factors and lipid profile wererecorded. Standard transthoracic evaluation was done and images from GLS2, 3 and 4 chambers view were recorded and analyzed with STE and strainimaging. Segmental strain (in17 segments from the left ventricle), GLS2chambers (represent the segments 4, 7, 10, 13, 15), GLS3 chambers(segments 2, 5, 8, 11, 13, 16), and GLS4 chambers (segments 3, 6, 9, 12, 14,16), and average GLS were assessed. Mann Whitney U test was used tocompare strain values.

Results: Thirty-eight patients and 21 controls were included. Average agewas 46.7/10 and 42/7 years respectively. Only one patient had historyof myocardial infarction and 13 had stroke. The prevalence of obesity (50%p0.012) and dyslipidemia (44.73% p0.001) was higher in PAPS groupthan the control. Only 4 patients had arterial hypertension under control. Thefrequency of other risk factors was similar between groups. Ventricularejection fraction was normal. In the PAPS group, myocardial segmental strainwas lower in apical segments (S13, S14, S16, S17), and in GLS2 (corre-sponding to inferior and anterior wall segments from the left ventricle)

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(p.0.03). The average of GLS was significantly lower in comparison withcontrols (p0.01).

Conclusion: Patients with PAPS without signs and symptoms of heartdisease had lower values of myocardial GLS than controls probably due tocoronary microcirculation abnormalities. Global longitudinal strain has apotential value in the assessment and treatment of myocardial dysfunction inPAPS patients.

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C5 Inhibitor rEV576 Ameliorates In Vivo Effects of AntiphospholipidAntibodies. Ana Laura Carrera-Marin1, Zurina Romay-Penabad1, SamuelMachin2, Hannah Cohen2, Wynne Weston-Davies3 and Silvia S. Pierangeli1.1University of Texas Medical Branch, Galveston, TX, 2University CollegeLondon, LOndon, United Kingdom, 3Varleigh Immuno Therapeutics, Ltd,London, United Kingdom

Background/Purpose: Murine models indicate involvement of thecomplement system in antiphospholipid (aPL)-mediated thrombosis.Complement split products (C5a and C3a) may enhance endothelial cell(EC) activation and pro-infllammatory/procoagulant states including tis-sue factor (TF) upregulation. rEV576 (coversin) is a recombinant salivaryprotein from the tick Ornithodoros moubata which protects it from attackby the hosts complement system (Nunn M A et al., J Immunol 174 (4),2084 (2005)). It is a small protein, which binds C5 inhibiting cleavage toC5a and C5b, the first component in the formation of MAC. Blockade ofthe complement cascade at the level of MAC generation is advantageousbecause it prevents the destructive effects of MAC while retaining theimmunoprotective role of upstream complement components (e.g. C3bopsonization and phagocytosis).Here we examined the effects of coversinon aPL-mediated thrombosis and upregulation of TF in an in vivo murinemodel.

Methods: C57BL/6J mice were injected i.p. twice with 0.5 mg of IgGfrom a patient with Antiphospholipid Syndrome (APS) or with controlIgG in normal human serum (NHS) preceded by i.p. injection of rEV5760.2 mg, calculated to totally inhibit C5 cleavage, or phosphate buffer(PBS) control. The size of induced thrombus was measured 72 h after thefirst injection. TF activity was determined in carotid homogenates.Anticardiolipin (aCL) and anti- 2glycoprotein I (anti-2GPI) antibodieswere determined in the serum of the mice by ELISA.

Results: see table

TreatmentThrombussize (m2)

TF carotid(pM/mg/ml)

aCL (GPLunits)

anti-2GPI(SGU)

IgG-APS PBS

2067 693 602.8 119.4 103.9 26.4 96.5 9.4

IgG-APS rEV576

767 179 () 176.7 38.9 () 114.2 15.7 104.6 13.9

IgG-NHS PBS

537 118 () 187.1 150.8 () 10 20

IgG-NHSrEV576

481 164 110.5 20.3 10 20

() p0.001 compared to IgG-APS PBS

IgG-APS PBS induced significantly larger thrombi and TF activitycompared to other groups. Mice treated with rEV576 and APS IgG hadsignificantly less thrombus and TF activity than those treated with PBS andAPS IgG. Mice treated with IgG-APS had high titers of aCL and anti-2GPIat induction of thrombus.

Conclusion: The data confirm involvement of complement activationin aPL-mediated pathogenesis and suggest that complement inhibitionmight ameliorate APS clinical manifestations.

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Pathogenic Effects of Antiphospholipid Antibodies Are Ameliorated InTissue Deficient Mice. Zurina Romay-Penabad1, Ana Laura Carrera-Marin1,Nigel Mackman2 and Silvia S. Pierangeli1. 1University of Texas MedicalBranch, Galveston, TX, 2University of North Carolina at Chapel Hill, ChapelHill, NC

Background/Purpose: Antiphospholipid (aPL) antibodies are associ-ated with thrombosis in patients with the Antiphospholipid Syndrome(APS). APL antibodies are thrombogenic in vivo and have been shown tocause upregulation and expression of tissue factor (TF) on culturedendothelial cells and increased procoagulant activity in monocytes in

vitro. Furthermore, monocytes from patients with aPL antibodies areknown to have increased procoagulant activity. However, whether TFplays a role on aPL-mediated thrombosis in vivo is unknown. Weaddressed that question by measuring the thrombogenic potential of aPLantibodies in mice with greatly reduced levels of TF in all tissues (low TFmice, mTF/, hTF), in an established mouse model of inducedthrombosis.

Methods: mTF/, hTF and the corresponding control mTF/,hTF in groups 5 mice were injected intraperitoneally (i.p.) twice witheither IgG from a patient with APS (IgG-APS) (500 g) or with controlIgG (IgG-NHS) (500 g). Seventy-two hours after the first injection asurgical procedure was performed to study thrombus dynamics. Theanticardiolipin (aCL) and anti-2 GPI titers in the serum of the mice weredetermined by ELISA.

Results: Thrombus sizes were significantly larger in mTF/, hTFmice injected with IgG-APS compared to these mice treated withIgG-NHS (1695 382 m2 vs. 546 48 m2; p.0001). Importantly,the size of thrombus in mTF/, hTF mice injected with IgG-APS(712 129 m2) was significantly smaller than the mean thrombus sizein mTF/, hTF injected with IgG-APS (1695 382; p.0001). Themean aCL and anti-2 GPI titers in the serum of mTF /, hTF andmTF/, hTF mice injected with IgG-APS were: 55 14 GPL and22 6 SGU and 53.3 19.3 GPL and 51 20 SGU at the time ofsurgery, respectively.

Conclusion: The data show that TF mediates aPL-induced thrombosisin vivo. Further studies will be performed to determine the cell types thatexpress TF and are responsible for thrombosis in APS.

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Patterns of Immunoglobulin-G Glycosylation Distinguish Different Clin-ical Phenotypes of Antiphospholipid Antibody Positivity. EdwardTarelli1, John S. Axford1, Ian Giles2, Charis Pericleous2, Silvia S. Pierangeli3,Yiannis Ioannou4, Anisur Rahman2 and Azita Alavi1. 1Sir Joseph Hotungcentre for Musculoskeletal diseases, St Georges University of London,London, United Kingdom, 2Division of Medicine/Centre for RheumatologyResearch, University College London, London, United Kingdom, 3Universityof Texas Medical Branch, Galveston, TX, 4University College London,London, United Kingdom

Background/Purpose: Polyclonal IgG and antiphospholipid (aPL)antibodies from patients with different clinical manifestations of theantiphospholipid syndrome (APS) have been shown to exert differentialeffects on signalling pathways and tissue factor activity in target cells.Interestingly, these biological effects were not distinguished by theirdegree of aPL binding which did not differ significantly between thedifferent APS subgroups.

Given that glycosylation is known to influence the biological activityof IgG, and that changes in IgG glycosylation patterns have been shownto predict clinical manifestations for various autoimmune diseases, weexamined whether differential glycosylation of IgG may be a factor indetermining the observed differences in the mechanism of the effects ofIgG from APS patients.

Methods: The glycosylation profile of IgG N-glycans, enzymaticallyreleased, from protein G purified IgG from four sets of 8 patients; APSwith pregnancy morbidity (PM) alone (aPL PM), vascular thromboses(VT) alone (aPL VT), aPLve patients without APS (aPL APS-) andhealthy controls (aPL- HC) was examined using Matrix Assisted LaserDesorption Ionisation Time-Of-Flight Mass Spectrometry (MALDI-TOFMS). IgG glycans were divided into three main groups based on thenumber of galactose residues: G0, G1 and G2. These biantennary complexglycans may be further modified by the presence/absence of fucose (F)and/bisecting N-acetylglucosamine (bis).

Results: There were no significant differences in aPL binding betweenthe different APS and aPL groups. In contrast, the glycosylation profileof IgG was found to be significantly different in the 4 groups examined(Figure). IgG from the APS patients had significantly higher ratios of totalG0:G2 compared with the aPL APS- patients (p0.038) and those fromaPL- HC (p0.002). On further, more detailed, analysis, the IgG frompatients with VT, which showed the most marked difference in totalG0:G2 ratio, could be differentiated from the PM group based onsignificant differences in the levels of G1F, G2, G2F and G1Fbis(p0.05).

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Conclusion: Our findings show that IgG from patients with diverseclinical manifestations of APS and aPL positive healthy controls exhibitdifferential patterns of glycosylation that were not predicted by differencesin aPL binding. Therefore, these glycosylation differences, which includethe degree of galactosylation as well as fucosylation, could be used as abiomarker to discriminate between patients with VT and PM, and mayprovide a better insight into the different mechanistic action of IgG in thesepatients.

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Role of Apolipoprotein B100 and Oxidized Low-Density Lipoproteinin Anti-beta2 Glycoprotein I Induced Tissue Factor Expression onMonocytes. Kotaro Otomo1, Tatsuya Atsumi1, Yuichiro Fujieda1, HisakoNakagawa1, Masaru Kato1, Olga Amengual1, Tetsuya Horita1, ShinsukeYasuda1, Masaki Matsumoto2, Shigetsugu Hatakeyama3 and TakaoKoike1. 1Department of Medicine II, Hokkaido University GraduateSchool of Medicine, Sapporo, Japan, 2Division of Proteomics, KyusyuUniversity Medical Institute of Bioregulation, Fukuoka, Japan, 3Depart-ment of Biochemistry, Hokkaido University Graduate School of Medi-cine, Sapporo, Japan

Background/Purpose: To explore plasma molecule involvement in thetissue factor expression induced by beta2 glycoprotein I dependent anti-cardiolipin antibody (aCL/2GPI) on monocytes.

Methods: Unknown beta2-glycoprotein I (2GPI) binding moleculesin plasma were screened by a proteomics technique using immunoaffinitychromatography and mass spectrometric analysis. To identify 2GPIbinding proteins, FLAG-tagged human 2GPI was constructed. Theexpression vector encoding FLAG-2GPI was transfected into HEK293Tcells, and the expression of full length FLAG-2GPI in the culturesupernatant was confirmed by immunoblotting. Human serum samplewith FLAG-2GPI was incubated and applied for affinity chromatogra-phy with anti -FLAG antibody-conjugated Sepharose beads. The purifiedfraction was subjected to SDS-PAGE, followed by a silver staining.Immunopurified proteins were analyzed by an online-nanoLC-MS/MS.Obtained MS/MS data were searched against nrNCBI database MASCOTalgorithm.

Results: Among many proteins detected in the spectrometry,ApoB100 was the only identified molecule as a candidate plasma protein.Since there was no significant binding between 2GPI and ApoB100 inELISA, oxidized LDL, containing ApoB100 as well as ox-Lig1 (a knownligand of 2GPI) in its molecule, was considered as a 2GPI-bindingmolecule in plasma.

The involvement of oxidized LDL was further investigated in aCL/2GPIinduced tissue factor expression on monocytes. RAW264.7, a monocyte cellline, was incubated with a monoclonal aCL/2GPI, WBCAL-1, in thepresence/absence of oxidized LDL. Cells were lysed and TF mRNA wasquantitated using Real Time PCR system. The presence of oxidized LDL

(100g/ml) and 2GPI markedly increased TF mRNA expression onRAW264.7 cells induced by WBCAL-1 (Fig). Oxidized LDL upregulated TFmRNA induction as well by purified IgG from APS patients with high titre ofaCL/2GPI.

Conclusion: Oxidized LDL was detected as a major 2GPI bindingplasma molecule by proteomics analysis. The presence of oxidized LDLupregulated aCL/2GPI induced TF expression on monocytes, suggesting theinvolvement of oxidized LDL in the pathophysiology of thrombosis inpatients with APS.

Figure. RAW264.7 cells were incubated with monoclonal aCL/2GPI (WBCAL-1) inthe presence of oxidized LDL. TF mRNA was quantitated by Real Time PCR.

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Circulating B Cells Subpopulations in Patients with AntiphospholipSyndrome. Lorena Alvarez-Rodriguez1, Marcos Lopez-Hoyos1, JaimeCalvo-Alen2, Rafael Barrio del1, Orlando Pompei1 and Victor M.Martinez-Taboada3. 1Hospital Universitario Marques de Valdecilla.IFIMAV, Santander, Spain, 2Hospital Sierrallana, Torrelavega, Spain,3Hospital Universitario Marques de Valdecilla-IFIMAV, Santander,Spain

Background/Purpose: Antiphospholipid syndrome (APS) is charac-terized by arterial and/or venous thrombosis and obstetrical complicationstogether with the production of antiphospholipid autoantibodies. Itspathogenesis remains to be elucidated, but the production of autoanti-bodies suggests that B cells may have some role in APS. Our aim was todescribe the peripheral blood frequency of B cells at different stages ofmaturation in APS.

Methods: Frequencies of B cells in peripheral blood of 25 APSpatients and 11 SLE (without APS) were determined by flow cytometry.As controls, 12 age- and sex-matched healthy subjects (HC) were used. Bcell subsets were identified with a combination of monoclonal antibodies(anti-CD5, -CD10, -CD19, -CD24, -CD27, -CD38, -CD138, -IgM andIgD) conjugated to different fluorochromes. Such a panel allowed us toidentify the following B cell subsets: immature, nave, double negative(DN), non-switched memory, switched memory and plasma cells.

Results: A significant decrease of circulating immature (p0.006) andnave (p0.003) cells in APS than in SLE patients was observed.However, non-switched (p0.001) and switched memory (p0.038) Bcells from peripheral blood of APS patients were increased as comparedwith SLE. No differences in circulating DN and plasma cells wereobserved between both disorders. In addition, nave B cells were higher inSLE patients than in HC whereas non-switched memory B cells werelower in SLE patients than in HC. No significant differences were foundin B cells between HC and APS patients.

Conclusion: Circulating B cells at a more differentiated stage werehigher in APS than in SLE, whereas immature B cells were higher in SLEthan in APS. These data point for a higher ability of B cells from SLE to

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mature in the periphery and to broad the spectrum of autoantigens they arereactive against. However, our data are only from the peripheral bloodcompartment and lack confirmation in bone marrow and germinal centres.

The present work was supported by grants from Roche (Spain) andIFIMAV.

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Circulating Cytokine Profile in Patients with Antiphospholipid Syn-drome. Lorena Alvarez-Rodriguez1, Marcos Lopez-Hoyos1, JaimeCalvo-Alen2, Rafael Barrio del1, Orlando Pompei1 and Victor M.Martinez-Taboada3. 1Hospital Universitario Marques de Valdecilla. IFI-MAV, Santander, Spain, 2Hospital Sierrallana, Torrelavega, Spain, 3Hos-pital Universitario Marques de Valdecilla-IFIMAV, Santander, Spain

Background/Purpose: Antiphospholipid syndrome (APS) is charac-terized by the combination of clinical manifestations (arterial and/orvenous thrombosis, and obstetrical complications) and the presence ofantiphospholipid antibodies. The role of cellular immunity in the patho-genesis of this syndrome remains unclear, although a shift to a Th1response, and an increased production of TNFa has been described. Theaim of the present study was to determine the peripheral blood cellularphenotype and the circulating cytokine profile in patients with APS.

Methods: Intracellular cytokine production was assessed in T cells(IFN-, IL-2, IL-4, IL-10, IL-17) and CD14 cells (IL-1, TNF-, IL-6)by flow cytometry in 27 patients with APS. As control groups we included17 age- and sex-matched healthy controls (HC) and 11 patients withsystemic lupus erythematosus (SLE). Patients with SLE had to be withSLEDAI4 (only treatment with antimalarials and/or low-dose cortico-steroids were allowed). Circulating cytokines were measured by Cytomet-ric Bead Array (CBA) in 13 patients with APS and 26 HC.

Results: Compared to HC, APS patients were characterized by adecreased frequency of circulating CD3IFN ex vivo (without stim-ulus). This decrease in circulating Th1 cells was accompanied by asignificant decrease in serum IL-12p70. Although we did not findsignificant differences in the expression of intracellular proinflammatorycytokines between APS and HC, serum levels of IL-6 were significantlylower in APS patients. Compared to HC, SLE patients were characterizedby a decreased frequency of circulating CD3IL-2 and CD3IFNex vivo (without stimulus). For circulating CD3IL-2, these differenceswere also significant compared to APS. Patients with SLE were charac-terized by a significant increased frequency of circulating Th17(CD4IL17CCR6 and CD4IL17IFN-) cells compared to HCand APS. Circulating CD4IL17IFN cells were also significantlyhigher in SLE compared to APS patients.

Conclusion: These preliminary results suggest that patients with APSshow a distinct functional profile in the peripheral cell compartment.Despite clinical remission or low disease activity, circulating Th17 cellsare increased in SLE patients but not APS patients.

The present work was supported by grants from Roche (Spain) andIFIMAV.

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A Systematic Analysis Confirms the Importance of Toll-Like Receptor 4,p38 Mitogen Activated Protein Kinase and Nuclear Factor Kappa-BActivation by Antiphospholipid Antibodies in Multiple Different CellTypes. Katie Poulton, Anisur Rahman and Ian Giles. University CollegeLondon, London, United Kingdom

Background/Purpose: Diverse experimental evidence exists impli-cating the activation of various different cell surface receptors andintracellular pathways by antiphospholipid antibodies (aPL). This evi-dence has been generated using a number of different cell types withvarying numbers of aPL from different sources and disease sub-types.This experimental variability has led to uncertainty in their interpretation.Therefore we have undertaken a systematic analysis of this evidenceimplicating aPL mediated activation of intracellular signalling pathwaysto interpret their relevance to the pathogenesis of the antiphospholipidsyndrome (APS).

Methods: A PubMed search was undertaken from 1966 up until May2011 using combinations of key signalling pathway words. Each publi-cation was systematically examined to note the following points; antibodytype and patient population, outcome measures and use of receptor/signalling pathway inhibitors, and cell type and origin.

Results: We identified 24 original studies implicating the importanceof aPL in activation of intracellular signalling pathways. The mostconvincing evidence from 21 in vitro and 3 in vivo studies in endothelialcells, monocytes, trophoblasts, platelets, and fibroblasts implicates tolllike receptor 4 (TLR4), p38 mitogen activated protein kinases (p38MAPK) and nuclear factor kappa B (NFkB) in mediating pathogenicintracellular effects of aPL. These consistent responses were confirmed inboth thrombotic and obstetric relevant cell types using human monoclonaland polyclonal antibodies and measured by various different outcomemeasures.

Conclusion: The main finding of our systematic analysis is thestriking degree of similarity between the conclusions of studies carried outby many different groups using different methods and cell types. A greaterunderstanding of how aPL activate these intracellular pathways willpotentially lead to the development of targeted agents to block thesepathways, thus reducing our reliance on anticoagulation as the onlycurrent treatment of APS.

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Anti-Phosphatidylserine/Prothrombin Antibody Titers Are StronglyCorrelated with Lupus Anticoagulant Assays in Patients with An-tiphospholipid Antibodies. Makoto Miyara1, Laurent Arnaud1, LaurentDufat1, Marie-Claude Diemert1, Annick Ankri1, Alexis Mathian1, JulienHaroche1, Du Boutin1, Pascale Ghillani-Dalbin1, Nathalie Costedoat-Chalumeau1, Silvia Casas2, Jean-Charles Piette1, Lucile Musset1 andZahir Amoura1. 1CHU Pitie-Salpetriere, Paris, France, 2InstrumentationLaboratory Werfen Group, Lexington, MA

Background/Purpose: Biological criteria for the antiphospholipidsyndrome (APS) diagnosis are the detection of either anticardiolipinantibodies (aCL), antib2GPI antibodies (ab2GPI) or lupus anticoagulant(LA). LA is strongly associated with thrombotic events in APS. Detectionof LA is complex as it requires several confirmatory steps, which may leadto delayed results. Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) have been recently associated with the presence of LA. However, itis still unclear whether aPS/PT titers correlate with LA assays.

Methods: 504 sera from 101 patients with either definite APSsyndrome (n82) or stable antiphospholipid antibodies (APL, either aCL,ab2GPI or LA; ACL levels 80 UGPL) without clinical APS manifesta-tions (n19) primarily collected for aCL, b2gPI and/or LA detection,were tested on a aPS/PT (IgGIgM) ELISA and on individual isotypeaPS/PT IgG and aPS/PT IgM ELISA assays (INOVA Diagnostics, SanDiego, CA). Correlations between titers of aPS/PT and those of aCL,ab2GPI, with Rosner index, dilute tissue thromboplastin inhibition ratio(dTTI) and dilute Russells viper venom time ratio (dRVVT) wereassessed using Spearmans non-parametric test. According to manufac-turer instructions, aPS/PT titers were considered positive when 30U/mL.

Results: aPS/PT were present in 12 of the 19 patients (63 %) with APLwithout thrombotic or obstetric events (4 with IgG isotype, 4 with IgMisotype and 4 with both) and in 69 of the 82 patients (84 %) with definiteAPS (19 with IgG, 11 with IgM and 39 with both isotypes).

Among the 81 patients with positive LA, 74 had aPS/PT (91 %) while7 did not (9 %). Among the 20 patients without LA, 16 did not haveaPS/PT (80 %) while 4 did (20 %). Presence of aPS/PT was significantlyassociated to the presence of LA (p0.0001 using a chi-square test). 10 of19 patients without APS had LA among whom 9 had aPS/PT (90%).Among the 9 other patients without LA, 3 had aPS/PT (33%). In the 82patients with APS, 68 patients had LA, among whom 65 had aPS/PT(96%). Among the 14 other patients without LA, 4 had aPS/PT (28%).

aPS/PT titers strongly correlated with Rosner index (r0.72,p0.0001), dTTI (r0.801, p0.0001) and dRVVT (r0.67, p0.0001).The ROC Curve yielded an excellent sensitivity of 84%, specificity of98%, and area under the ROC Curve of 0.92 for detecting the presence ofLA using an aPS/PT cut-off titer of 53 U/mL.

Conclusion: We confirmed that the presence of aPS/PT antibodies(either IgG isotype, IgM isotype or both) is strongly correlated with thepresence of LA. Furthermore, titers of aPS/PT were strongly correlatedwith Rosner index, dTTI and dRVVT. Our data suggest that aPS/PT(IgGIgM) ELISA assay could be a good alternative test for the detectionof LA.

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Presence of Anti-Phosphatidylserine/Prothrombin Antibodies with BothIgG and IgM Isotypes May Be Associated with the Occurrence ofCatastrophic Antiphospholipid Syndrome in Patients with Antiphospho-lipid Antibodies. Makoto Miyara1, Laurent Arnaud1, Laurent Dufat1, Marie-Claude Diemert1, Annick Ankri1, Alexis Mathian1, Julien Haroche1, DuBoutin1, Pascale Ghillani-Dalbin1, Nathalie Costedoat-Chalumeau1, SilviaCasas2, Jean-Charles Piette1, Lucile Musset1 and Zahir Amoura1. 1CHUPitie-Salpetriere, Paris, France, 2Instrumentation Laboratory Werfen Group,Lexington, MA

Background/Purpose: Catastrophic antiphospholipid syndrome (cAPS)is a life threatening condition with simultaneous thrombosis in multipleorgans that can occur in patients with antiphospholipid antibodies (APL).Predictive biological parameters for cAPS have not been defined yet.Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) of either IgG orIgM isotypes or both have been recently associated with the presence of LA.It has not been determined whether aPS/PT isotypes are correlated to clinicalfeatures of antiphospholipid syndrome (APS).

Methods: 157 sera from patients with cAPS (n29), 58 sera frompatients with APS (n29) and 31 sera from patients with stable antiphos-pholipid antibodies (APS, either aCL, ab2GPI or LA; ACL levels between 25and 75 UGPL) without clinical APS manifestations (noAPS; n19), primar-ily collected for aCL, b2gPI and/or LA detection, were tested on individuali