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Natural Autoantibodies as Specific Immune Markers
of the Disease
Alexander PoletaevMedical Res. Ctr. «Immunculus»
P.K.Anokhin Res. Inst. of Normal Physiology
Moscow, Russia
2) Pre-disease correction
1) Pre-disease diagnostic
Crucial question (evaluation of effectiveness of the used medical paradigm):
Reparative Medicine
(The disease now presented should be
now treated)
Preventive Medicine(To reveal the pre-disease changes
– To prevent the disease)
In general ANY Medicine is imply prevention/ Just prevention of pre-term
death
If the biological limit of human life calculated nearly as 120-150 years - how many years (30? 50?) – an averaged person lose unjustified?
Individual genetic analysis do not have alternative for prediction of “monogenic diseases” (example: phenylketonuria). On the other hand the prediction of polyfactor diseases (most cancers, cardio-vascular diseases, etc.) are out of the field of responsibility of the molecular genetic
What can be proposed for early prediction of the most diseases?
Soon after the development of ELI-Test technology was
began (ELI-Test - from Enzyme-Linked Immuno-Tests)
ELI-Tests are based on analyses of the changes in profiles of the marker auto-Abs
ELI-Test methods were intend for a mass-scale prophylactic medical examination
Chernobyl Disaster (1986)
ELI-Test Technology:
It is based on ability of the Immune System to be natural “Magic Mirror” reflecting the health state of individual; including the beginning of any pathology (future disease) as well as the disease presented now
ELI-Test Technology was intended for:
a) Early revealing of any pathology at the beginning stages
b) Verification of the disease in not quite clear cases
c) Monitoring of the health state changes during the treatment course
ELI-Viscero-Test (24)
Marker sign of the Small Vessel’s
Vasculitis
Profiles of auto-Abs in
the blood serumNB: not the concentration!
Kidney insufficiencyHeart insufficiencyChronic obstructive lung diseaseTrophic ulcersStroke
Future problems
Case reportM.,42 y.o., no complains, clinically healthy
Habitual (bacteriologist’) views:
1) Predestination of the ISYS is the WAR and destruction
2) There are no place for Natural Autoimmunity in healthy organism!
Physiological view: Not War, but
Peace (homeostasis) is predestination
of the ISYSIts main functions are:
Autoidentification, Autoclearance, Autoreparation,
Ilya I.Mechnikoff(1845-1916)
Polly Matzinger (2002): Any tissue’s
injury accompanied by the transitory autoimmune reactions against tissue antigens.
It is physiological response to the damage. It provides:
a) Activation of the clearance (from dying cells and debris);
b) Activation of the tissue regenerative processes
The phenomenon of natural immune
autoclearance is the ground for ELI-Test
Diagnostic Technology
Principles of Autoclearance
Macrophages are blind for Self AG (absent receptors for self-AGs, but presented receptors (Fc-Rc) for AG-Abs complexes)
Antibodies play role of the pointing the finger (“signature”) for AGs whose should be “eaten” by macrophages
Fc-Rc
Macrophages + Auto-Abs (together) represents the Main Instrument of Autoclearance
Self-AG Ab
AG marked by Ab
> 100 milliards cells died in each healthy human daily (Silverman, 2011) This hazard “garbage” must be utilizingpermanently
ISYS is a house-keeper!
(neither a policeman nor KGB’s agent)
AUTOCLEARANCE has based on the phenomena of Natural Autoimmunity
Necessity in Autoclearance rise prominently if the pathology begins (in any organ and tissue)
Activation of Autoclearance = Activation of Sanogenic Autoimmunity
b) Motor or mental defects, or death
а) Complete rehabilitation
The transitory rise of “neurotropic” auto-Abs is a good prognostic sign
Absence of autoimmune reaction mean a bad prognosis
STROKE: If there is no activation of Auto-immunity after stroke – it means the clinical prognosis for the patient is rather bad (E.I.Gusev et al., 2004-2008)
Feed-back principle: (Experiments 1980-1985) Elevation of any of Self-AG (that is rise of its availability for the Immune System) lead to the rise of production of respective auto-Ab
“Conception of Immuno-Chemical Homeostasis of the Organism”
I.E. Kovalyov (1985)
Activation of the cell’s death (apoptosis)
Rise of expression or secretion of macromoleculesAdministration some AG in non-physiologic concentration
The Main Causes of AG elevation:
The phenomenon does not mean the autoimmune pathogenesis of the disease: It is a reflection of the compensatory elevated expression of (abnormally functioning) Ins-receptors
Pre-Diabetes: Rise of auto-Abs against insulin receptors as a marker of pre-diabetes and early stages of diabetes
type II Abs against Ins-Rc
Case report
“Autisic profiles” of the serum auto-Abs (ELI-Neuro-Test)
GFAP (~50% of cases)
Ach-R (~60% of cases)
5HT-R (~70% of cases)
Do the changes reflects abnormalities in expression of according receptors? Or what? (autoimmune
aggression?)
?
Besides elevated a-Abs against V-gated Ca-Ch, S100, DA-R (may be seen in ~20-
30% of cases)
-40,0
-20,0
0,0
20,0
40,0
60,0
ChGT
dsDN
A
b2-G
P
Collag
en
Rheu
mofac
tor
Insulin
Thyro
glob. S1
00
Spr06
TrM03
ANCA
KiM05
Анти-ХГЧ синдром
Example of iatrogenic disease: Iatrogenic Anti-Chorionic
Gonadotropin Syndrome in woman induced by the IVF procedure
(steady elevation of Ab against ChGT in more then 60% women after IVF with using of “Pregnyl” or “Choragon”)
Anamnesis Anti-ChGT Syndrome was diagnosed after preceded IVF (unsuccessful).
The Last Pregnancy:
• Placental malformation;
• Stillbirth at 22-24 weeks
Case report
ELI-Neuro-Test
ELI-ANCOR-Test
ELI-Pulmo-Test
ELI-Nephro-Test
ELI-SIC-Test
ELI-Repro-Tests
Adopted by The Ministry of
Health:
SIR SGLTPG
LGC
QVVKAE
GSCSPL
DNAIn
sulin
b2GPI
PPACPD
KEENFN
AGAADD
S100AFP
SPRColl
agen
AB_Glyc
erin
LLP_g
c
LLP
AB_new
NNS_PAA
NNS_gc
KLM_g
c
KLM Angios
tatin
-100
-50
0
50
100
150
200
250
300
Профиль аутоантител в сыворотке пациента (55Cr)
55_2
+2s
-2s
Auto-Ab profiles in patient with early stage of the breast cancer
Shading zone is equivalent
of “Two Sigmas”
(deviation from average normal
data)
ELI-Onco-Test dataCase report
Frequency of the organ pathology which has been (left bars) or not been (right bars) associated with the changes in serum contents of corresponding auto-Ab (General number of observations: n = 7308; p < 0.05 … p < 0.001)
From Dissertations:FEIGINA A.A. – Clinical and neuroimmune aspects of epilepsy after stroke. Moscow, 2008.LUCENKO Y.V. – Serum content of cardiospecific antibodies in children with heart arhitmias. Moscow, 2010.OSIPENKO Leeza – System dynamics in early health technology assessment: prenatal screening technology
(ELI-P Complex). Stevens Institute of Technology, Hoboken, NJ 07030, 2005.GENERALOVA G.A. – Renal autoantibodies in healthy state and during kidney’s pathology, Moscow, 2002.GNEDENKO B.B. – Immunochemical aspects of diabetic fetopathy. Moscow, 2001. KLUCHNIKOV S.O. – Ecological pathology in children. Complex investigations, Moscow, 1999.
Steady excess of anti-renal Abs and kidney's malfunction (p < 0.01)
0
100
200
(A) (B)
Steady rise of ANCA: corelation with vascular problems (p < 0.01)
0
50
100
150
200
(A) (B)
Excess of auto-Abs against GFAP (A) and seizure simptomes (p < 0.05)
0
5
10
15
20
25
30
35
40
(A) (B)
Auto-Immunity may be compared
with Double-faced Janus:
In the most cases it behaves like Good Dr. Jekill, but sometimes like Bad Mr.
Hyde
(Secondary) Primary injuries
lead to activation of specific adaptive autoimmune reactions (raising clearance and regeneration)
(Primary)
Activation of auto-immunity (not rela-ted to the needs of organism) leads to the pathology in the different organs
NATURAL AUTOIMMUNITY - PATHOGENIC AUTOIMMUNITY
Rose NR, Witebsky E - Thyroid autoantibodies in thyroid disease, Immunology, 1956; 76: 417-457
Auto-Ab as a markers of a disease (in future and now presented)
Ernst Witebsky Noel Rose
X-Ray, MRI, etc. provides the possibility to reveal the disease PRESENTED NOW
Infiltrative Tuberculosis of the left lobe of the lungs in stage of disintegration
It became possible to reveal
the disease even before its manifestation
• Do you wish to know?
• What should we to
do…?
Questions arise:
A man needs not only in a health. But he needs nothing if his health is poor
Socratus (469 – 399 B.C.)
Could the nutriciology, physiotherapy, homeopathy, acupuncture, etc. become an instruments for pre-disease health state correction?
(Lecture-2)
The Mother and the Child relations in the “Mirror of
AutoImmunity”
dsDNA
APS syndrome
ChGT
TrM-03
b2-GP I
Ig-Fc (RF)
S100
Insulin
Active intracellular infection
Zygote implantation and Placentation
Chronic inflammation
Abnormalities in apoptosis and Neural Tube
Collagen Scars/synechias forming
Platelets abnormalities
Vasculites and vasculopathiesАNCA
Diabetic fetopathy; Endothelial dysfunction
Thyroid pathology, Embriotoxic effects
Endometritis
Kidney pathology
Thyroglobulin
SPR-06
KiM-05
ELI-P-Complex (the first one elaborated after Chernobyl)
Profiles of auto-Abs in woman blood serumNB: not concen-tration
-40,0
-20,0
0,0
20,0
40,0
60,0
ChGT
dsDN
A
b2-G
P
Collag
en
Rheu
mofac
tor
Insulin
Thyro
glob. S1
00
Spr06
TrM03
ANCA
KiM05
Анти-ХГЧ синдром
Example iatrogenic disease: Iatrogenic Anti-Chorionic
Gonadotropin Syndrome in woman after IVF procedure
(steady elevation of Ab against ChGT in more then 60% women after IVF with using of “Pregnyl” or “Choragon”)
Anamnesis Anti-ChGT Syndrome was diagnosed after preceded IVF (unsuccessful).
The Last Pregnancy:
• Placental malformation;
• Stillbirth at 22-24 weeks
Case report
70,4%
29,6%
Anti-S100 Abs in HPV-infected women (E.N.Koshel et al., 2007-2010)
Elevated Abs against S100
Normal level of Abs against S100
(Vaccination against HPV in this context also may become problematic if lead to abnormal rise of Abs against S100)
10-12-times rise of the risk of neurology deviations
8-10-times rise of the risk of miscarriages and stillbirths
“Classic” investigation of a serum sample for auto-Abs to beta2-GPIdid not reveal any signs of APS because of individual immune supression
Investigation of the “profiles” of multiple auto-Abs permit to reveal a typical sign of APS (in spite of immune suppres-sion); red line above the patient data – upper limit of an averaged population immune reactivity
Case report
1-10
-8
-6
-4
-2
0
2
4
-7% from “population norm”
Satisfactory Results of a New Pregnancy in Women with a Habitual Miscarriages:
(A) Pre-gestational treatment was controlled by measuring of auto-Abs
(В) Without control of auto-Abs
0
10
20
30
40
50
60
70
80
A B
~ 70%
~ 12%
Six “storks” or one?!
Experimental modeling of Multiple Sclerosis:
1) In a normal state it is rather difficult to induce the disease by injections of MBP;
2) The disease can be easily induced if MBP injected upon inflammatory background
Immune activation is a factor of risk for post-vaccinal
complications
ELI-Vaccina-Test (are there Immune Deviations?)
-50,0
-30,0
-10,0
10,0
30,0
50,0
70,0
90,0
ds-DNA IF-g IF-a b2-GP Fc-Ig Coll
Used AGUsed AG (adsorbed in the wells)(adsorbed in the wells)
Results (profiles)Results (profiles) Normal rangesNormal ranges
dsDNAdsDNA --5500 -20…+10-20…+10
Interferon-gammaInterferon-gamma --4488 -20…+10-20…+10
Interferon-alphaInterferon-alpha +70+70 -20…+10-20…+10
betabeta2-2-Glycoprotein IGlycoprotein I --3232 -20…+10-20…+10
Fc-IgGFc-IgG ++9922 -20…+10-20…+10
Collagen IICollagen II --6644 -20…+10-20…+10
Case report
Maternal Immune Imprinting (a la Konrad
Lorenz) Transplacental transfer of maternal IgG Abs
Tuning of the lymphocytes of the fetus and newborn
Prominent similarity between the immune features of mother and her child (not father – child)
This phenomenon is the base for:
(а) Specific resistance to the infections before the direct contact with microbes;
(б) Sometimes it may be cause for the development of pathology of the same organ (heart, kidney, etc.) as it was in his mother
Maternal ELI-Viscero-Test data
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
-90
-80
-70
-60
-50
-40
-30
-20
-10
010
2030
4050
6070
8090
Норм
аПо
гран
ичны
е отк
лоне
ния
Дост
овер
ные о
ткло
нени
я
Ab to KiM-05 Ab to
Rc-TSH
Moderate proteinuria and decreasing of the blood TSH content was found in child (boy 2,5 y.o.)
Clinical case report: Woman, 36 y.o., Complains: fatigability, periodical elevation of blood pressure.
ELI-Viscero-Test data: 1) Signs of pathology in kidneys; 2) Signs of Thyroiditis
The Results of Additional Investigations: 1) Moderate bacteriuria and leucocytouria. Weak signs of pelvic inflammation; Spinal protrusions.
Diagnosis: Chronic pyelonephritis (subclinical); hypertension (early stage); Thyroiditis (early stage); Spinal protrusions
Case report
“Autisic profiles” of the serum auto-Abs (ELI-Neuro-Test)
GFAP (~50% of cases)
Ach-R (~60% of cases)
5HT-R (~70% of cases)
Besides elevated a-Abs against V-gated Ca-Ch, S100, DA-R (may be seen in ~20-
30% of cases)
Maternal Immune Imprinting can be the reason for the development of some forms of mental/neurology deviations in the children
?
GFAP
Emotional dysfunctions
NF-200
AChRc(n)
S100
MBP
GABA-Rc
DOPA-Rc
Gliosis (post-traumatic, post-ischemic)
Nervous fibers degenerative changes
Demyelinating diseases
Epilepsy, Psychoses
(V)Ca-chanel Myastenic syndromes
Myastenic syndromes
Epilepsy, Stroke Glu-Rc
Schizophrenia, Parkinson disease
Emotional dysfunctions, Bipolar disease
Opiate system dysfunctions
Opiate system dysfunctions
5HT-Rc
-Opiate Rc
Endorphine
ELI-Neuro-Test
73%
16%
11%
Child Health State (n = 589)
Healthy Children
Small deviations in a Health State
Poor Health State
17%43%
40%
45%
55%
Normal profiles of auto-Abs at pregnancy
The Health State of Child at age 3-4 years is directly related to the Immune State of Mother during her pregnancy
(Zamaleeva, Kluchnikov, 2002)
74 %
16 %
0 %
Moderate deviations in profiles of auto-Abs
Prominent deviations in profiles of auto-Abs
“The child’s health is
formed in the mother’s
Womb”
Professor Leonid
Persianinov:
Lets keep in mind Persianinov’s sentence