Date post: | 11-Jan-2016 |
Category: |
Documents |
Upload: | margaretmargaret-king |
View: | 216 times |
Download: | 1 times |
Systemic Lupus Erythematosus
By: Selena Davis Capstone Presentation
Selena J. DavisHometown: Philadelphia,
Pennsylvania
Major: Biology
Class: Senior
Career Plan: Graduate School
What is the common link?
What is Systemic Lupus Erythematosus?
An autoimmune disease in which the immune system produces antibodies (autoantibodies) to cells and tissues within the body; leading to inflammation and tissue damage.
Joints, skin, brain, lungs, kidneys, and blood vessels are most often affected.
Summary of Antibody Synthesis
B-Cells In SLEActivate and produce
autoantibodiesAntibodies attack patient’s cells.Abnormal cells not deleted by
apoptosis?
T-CELLS (lymphocytes)Play key roles in B-cell activation.
Background InformationAutoantibodies (mainly anti-
nuclear antibodies) bind to double-stranded DNA; causing inflammation in tissues and organs throughout the body.
Disease in young women tends to be more severe (multiple organs involved)..
Lupus is more common in African Americans, Hispanics, Asians, and Native Americans than Caucasians.
Background Info (cont.)Diagnosis is difficult in mild
cases.
Treatments usually involve drugs to reduce inflammation and suppress immune system responses.
High morbidity and mortality rates are due to late diagnosis, lack of medical care, lack of effective treatments, and no standard therapeutic regimens.
Pathology – Highly Variable
Diagnosis
The American College of Rheumatology (ACR) uses a standard classification scheme requiring 4 of 11 criteria to meet the clinical diagnosis of lupus, although this standard often excludes early and mild cases of lupus.
Diagnosis - Continued 1. Characteristic rash
across the cheek or “butterfly rash”
2. Discoid lesion rashes
3. Light sensitivity
4. Oral ulcers
5. Arthritis
6. Inflammation of membranes in the lungs, the heart, or the abdomen
7. Evidence of kidney disease
8. Evidence of severe neurologic disease
9. Blood disorders, including low red and white blood cell and platelet counts
10. Immune abnormalities
11. Positive antinuclear antibody (ANA)
Laboratory Diagnostic TestingAntibody tests, including
antinuclear antibody (ANA) panel
CBC (complete blood count)
Chest X-ray
Kidney biopsy
Urinalysis
Review 1: Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden
Objective: The aim of this study is to summarize data on SLE incidence and prevalence in the USA, Europe, Asia, and Australia. This was the most extensive study done on lupus worldwide.
Method: Data was collected from electronic resources (PubMed and MedLine) and medical journals was analyzed to identify published studies on the incidence and prevalence of lupus from 1950–early 2006.
Results: There were significantly higher SLE incidences among non-whites compared to whites. The lowest overall incidence estimates were reported in Iceland and Japan, and highest in the USA and France. It showed higher SLE prevalence rates in non-white racial groups when compared to whites.
Conclusions: The study showed disparities in SLE incidence and prevalence worldwide when specific racial and ethnic groups were analyzed.
Worldwide Incidence
Worldwide Prevalence
Reviews 2 and 3: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of
Belimumab (Benlysta) in Patients With Active Systemic Lupus Erythematosus
(Summary of 2 Similar Studies) Objective: To assess the safety, tolerability, biological
activity, and effectiveness of Benlysta in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE).
Benlysta is a monoclonal antibody that binds to B cell activating factor (also called B lymphocyte stimulator); inhibiting B cell synthesis
Methods: 449 Patients with lupus were prescribed Benlysta (1, 4, or 10 mg/kg) or a placebo in a 52-week study.
B cell activities were measured and compared to patient’s overall health outcomes.
Results: Treatment with Benlysta resulted in 63–71% depletion of naive, activated, and CD20+ B cells and a 29.4% reduction in lupus autoantibody concentrations by week 52. The rates of adverse events (AEs) and serious AEs were similar in the Benlysta and placebo groups.
Conclusion: Benlysta was biologically active and well tolerated. Benlysta’s effect on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to Benlysta therapy plus SOC than SOC alone.
B cell Activities with Benlysta
The Cause
UNKNOWN
Genetic
Environmental
Hormonal factors
Treatments
Mainly used to reduce inflamation.
Benlysta (belimumab) was approved in (2011) to treat lupus ($35,000/year)
Corticosteriods (anti-inflammatory)
Conclusion Research has shown that lupus
appears to have no single cause. Genetics, environment, hormones, and other factors are being investigated.
Reducing inflammation in major organs is the major standard of care used.
More research is needed to better understand what events cause B cells to react against normal cells and tissues in the body.
References Michael P. Cancro DPDC, and Munther A. Khamashta. 2009. The role of B lymphocyte stimulator (BLyS) in
systemic lupus erythematosus. The Journal of Clinical Investigation 119(5):1066-1073.
M. J. Leandro GC, J. C. Edwards, M. R. Ehrenstein, and D. A. Isenberg. 2005. B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients Rheumatology 44(12):1542-1545.
Lipsky ACGaPE. 2003. B cell abnormalities in systemic lupus erythematosus. Arthritis Reasearch & Therapy 5(4):S22-27.
Laurent Chiche NJ, Guillemette Thomas, Nathalie Bardin, Charleric Bornet, Albert Darque, and Julien Mancini. 2012. New treatment options for lupus – a focus on belimumab. Therapeutics and Clinical Risk Management 8:33-43.
Danchenko N, Satia JA, Anthony MS. 2006. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 15(5):308-318.
Center UoMM. Systemic lupus erythematosus - Causes [Internet]. Available from: http://www.umm.edu/patiented/articles/what_causes_systemic_lupus_erythematosus_000063_2.htm
Jr. WCS. Systemic Lupus Erythematosus [Internet]. Available from: http://www.medicinenet.com/systemic_lupus/article.htm
Prevention CfDCa. Systemic Lupus Erythematosus (SLE or lupus) [Internet]. Available from: http://www.cdc.gov/arthritis/basics/lupus.htm
Sanz I, Yasothan U, Kirkpatrick P. 2011. Belimumab. Nature Reviews Drug Discovery 10(5):335-336.
Graciela S Alarcón GM, Ana M Bertoli, Barri J Fessler, Jaime Calvo‐Alén, Holly M Bastian, Luis M Vilá, and John D Reveille. 2007. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Annals of the Rheumatic Diseases 66(9):1168-1172.
Judith A James KMK, A Darise Farris, Elizabeth Taylor-Albert and Thomas J A Lehman. 1997. An Increased Prevalence of Epstein-Barr Virus Infection in Young Patients Suggest a Possible Etiology for Systemic Lupus Erythematosus. The Journal of Clinical Investigation 100(12):3019-3026.
Wallace DJ SW, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong ZJ and Freimuth WW. 2009. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheumatology 61(9):1168-1178.
Special Thank you.
Dr. Whittaker- Capstone MentorDr. Roy Coomans – Academic
AdvisorBiology Department Faculty
Questions?