Presentation: Seminar for physicians, Roma, Nov. 2013

1. Natural Autoantibodies as
Specific Immune Markers
of the Disease
Alexander Poletaev
Medical Res. Ctr. «Immunculus»
P.K.Anokhin Res. Inst. of Normal Physiology
Moscow, Russia

2. 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?

3. 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?

4. 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)

5. 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

6. 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

7. ELI-Viscero-Test (24)
Marker sign of
the Small Vessel’s
Vasculitis
Profiles of
auto-Abs in
the blood
serum
NB: not the
concentration!
Kidneyinsufficiency
Heartinsufficiency
Chronicobstructivelungdisease
Trophiculcers
Stroke
Futureproblems
Case report
M.,42 y.o., no complains,
clinically healthy

8. 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 ISYS
Its main functions are: Autoidentification,
Autoclearance, Autoreparation,
Ilya I.Mechnikoff
(1845-1916)

9. 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

10. The phenomenon of
natural immune
autoclearance is the
ground for
ELI-Test Diagnostic
Technology

11. 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 utilizing
permanently

12. 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

13. 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)

14. 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 macromolecules
Administration some AG in
non-physiologic concentration
The Main Causes
of AG elevation:

15. 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

16. “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)

17. -40,0
-20,0
0,0
20,0
40,0
60,0
ChGT
dsDNA
b2-GP
Collagen
Rheumofactor
Insulin
Thyroglob.
S100
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

18. ELI-Neuro-Test
ELI-ANCOR-Test
ELI-Pulmo-Test
ELI-Nephro-Test
ELI-SIC-Test
ELI-Repro-Tests
Adopted by The
Ministry of Health:

19. SIR
SG
L
TPG
LG
C
Q
VV
KAE
G
SC
SPL
DNA
Insulin
b2G
PI
PPA
CPD
KEE
NFN
AG
A
ADD
S100
AFP
SPR
Collagen
AB_G
lycerin
LLP_gc
LLP
AB_new
NNS_PAA
NNS_gc
KLM
_gc
KLM
Angiostatin
-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 daTa
Case report

21. 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)
Steadyrise 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)

22. 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

23. 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

24. 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

25. • 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?

26. (Lecture-2)
The Mother and the Child
relations in the “Mirror of
AutoImmunity”

27. 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
serum
NB: not
concen-
tration

28. -40,0
-20,0
0,0
20,0
40,0
60,0
ChGT
dsDNA
b2-GP
Collagen
Rheumofactor
Insulin
Thyroglob.
S100
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

29. 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

30. “Classic” investigation of a serum
sample for auto-Abs to beta2-GPI
did 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
-7% from “population norm”

31. 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?!

32. 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

33. 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

34. 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

35. Maternal ELI-Viscero-Test data1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
-90-80-70-60-50-40-30-20-100102030405060708090
НормаПограничныеотклоненияДостоверныеотклонения
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

36. “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
?

37. 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
µ-Opiate Rc
Endorphine
ELI-Neuro-
Test

38. 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

39. “The child’s
health is
formed in
the mother’s
Womb”
Professor Leonid
Persianinov:
Lets keep in mind
Persianinov’s sentence