[Early detection of cancer--genetics or immunology?].

The earliest (in preclinical stages) detection of malignant tumor process is a key factor in successful treatment of cancer. What methods and approaches are most suitable for this purpose? The paper presents current understanding of the biological basis of the process of malignancy and analyzes the comparative opportunities and prospects for early detection of cancer using molecular genetics and immunochemical approaches.

[THE CHARACTERISTICS OF SYSTEMIC AND LOCAL IMMUNE REACTIONS UNDER HABITUAL NON-CARRYING OF PREGNANCY].

The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P-Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses. In women with non-carrying of pregnancy polyclonal immunosuppression, increased level of embriotoxic auto antibodies to Fc- fragment of immunoglobulin, insulin and thyroglobulin are detected. The immune histochemical analysis established expressed decreasing of amount of progesterone receptors of stromal elements of endometrium after spontaneous abortion. The activation of killer activity of decidual lymphocytes under habitual non-carrying of pregnancy was detected too. The positive dependency was established between: expression of progesterone receptors in glandular cells of endometrium and level of anti-spermatic antibodies in blood serum; expression of progesterone receptors in stroma and level of antibodies to human chorial gonadotropin; expression of receptors of estrogens in stroma and level of antibodies to Fc-fragment of immmunoglobulines. The study data permits affirming that evaluation of level of regulatory auto-antibodies is informative at examination of woman after episode of non-carrying of pregnancy. The production of antibodies has direct relationship with pathological processes in endometrium and it can be one of criteria of completeness of pre-conceptional preparation.

[Comparative analysis of the serum level of autoantibodies as a diagnostic tool of myocardial inflammatory diseases].

AIM: To assess whether the serum levels of autoantibodies (auto-Abs) interacting with myocardial and vascular wall antigens might be used for the differential diagnosis of myocardial inflammatory diseases. Subjects and methods. Seventeen patients with morphologically documented myocarditis were examined. A comparison group comprised 9 patients with acute myocardial infarction (AMI). A control group included 18 apparently healthy individuals and 8 patients with chronic erosive gastritis (CEG). Serum auto-Abs levels were estimated by the ELI test systems standardized for enzyme immunoassay. RESULTS: The individual profiles that reflect relative changes in the levels of 16 study auto-Abs and characterize the integral autoreactivity of a patient have clear intergroup differences. Using the profiles of auto-Abs could confirm the diagnosis of myocarditis in 94% of cases or assign the patient to a group of apparently healthy individuals. The informative value of the method in patients with AMI and CEG was 81.8 and 87.5%, respectively. CONCLUSION: The proposed method may be used for the noninvasive screening diagnosis of myocardial inflammatory diseases.

Immunophysiology versus immunopathology: Natural autoimmunity in human health and disease.

Based on the analysis of literature and our own data, some key concepts of natural autoimmunity are reviewed from the point of the Pathophysiology: immunological regulation of homeodynamics, physiological autoimmunity versus autoallergy and predictive roles of natural autoantibodies are discussed. Hypothesis of Immunculus and principle of Immunacea are correlated to some of clinical examples with immunopathological data and the perspectives of autoimmunomics are described.

[Autoimmunity and autoimmune syndrome: norm and pathology].

Multicomponent analysis of variations of serum marker antibodies is an efficacious tool for preventive (pre-clinical) diagnosis of immune disorders causing serious diseases. Successful development of this method may lead to revision of the approaches accepted in modern medicine and facilitate practical transition to the prognosis-prevention paradigm. The study of antibody spectra reflecting individual genetic and epigenetic features provides a basis for prognostication of health and pathological conditions. We believe that in most cases early diagnosis of reversible pathologic processes their further development can be arrested which provides a real opportunity to preserve health.

[Natural neurotrophic IgG autoantibodies in the blood serum of patients with different clinical outcomes after ischemic stroke].

Recent studies revealed a role of natural neurotrophic IgG autoantibodies (NNAA) in the trophic supply of nervous tissue and modification ability of neuronal networks. Changes of the NNAA level likely may reflect direction (compensation, decompensation) of cytochemical and morphologic alterations of nervous tissue in acute focal ischemia, thus, having certain prognostic value. To assess the dynamics of NNAA in the blood serum on 3, 7, 14 and 21 days after ischemic stroke and 3 months after the disease, 84 patients (mean age 68+/-10 years) with first-ever stroke in the system of internal carotid artery were studied. NNAA immunoreactivity to four nervous tissue proteins, S100b, GRAP, MP-65, NGF, was conducted using ELIZA method. Patients' outcomes were assessed with the Barthel Index and NIH on the 3rd month of the disease. In the acute period of stroke, the changes of immunoreactivity, comparing to controls, were found in 95% o cases (p<0,01), the level of NNAA pathologically increased or decreased. The increase of NNAA level was revealed in 45 patients (56% cases) with satisfactory clinical rehabilitation on 7-14 days (p<0,0001) with the following normalization of these parameters to the 21st day. In case of unfavorable outcomes, the prolonged increase of the NNAA level or decrease of immunoreactivity (p<0,0001) was found in 44% of cases. The changes of NNAA level were observed in 60 patients on the 3rd month of the disease, i.e. the protracted decrease of immunoreactivity was found in 42 patients and increase - in 18 cases (p<0,01). The quantitative changes of NNAA likely indicate the adaptive-compensative reaction of the immune system. The character of immunoreactivity changes is related to reparative neuroplasticity and may be of prognostic value.

Dialectics and implications of natural neurotropic autoantibodies in neurological disease and rehabilitation.

The role of natural idiotypic (Id-Abs) and anti-idiotypic (AId-Abs) autoantibodies against neuroantigens observed in different neurological disorders is not fully understood. In particular, limited experimental evidence has been provided concerning the qualitative and quantitative serological response after acute injuries of the central nervous system or during chronic mental diseases. In this study, we analyzed the specific Id-Abs and AId-Abs serological reactivities against 4 neuro-antigens in a large population of patients with ischemic stroke, schizophrenia, as well as healthy individuals. Patients with ischemic stroke were tested at different time points following the acute stroke episode and a correlation was attempted between autoantibodies response and different patterns of functional recovery. Results showed variable and detectable Id-Abs and AId-Abs in different proportions of all three populations of subjects. Among patients with different functional recovery after ischemic stroke, a difference in time-related trends of Id-Abs and AId-Abs was encountered. Our observations suggest that changes in the production of natural neurotropic Abs may engender a positive homeostatic, beside a possible pathogenic effect, in specific neurological disorders.

The immunological homunculus (immunculus) in normal state and pathology.

The immunculus is considered as the system (general network) of constitutively expressed natural autoantibodies against different extracellular, membrane, cytoplasmic, and nuclear self-antigens (ubiquitous and organ-specific). It is specially noted that the repertoires of natural autoantibodies are surprisingly constant in healthy persons, independent of gender and age, and characterized by only minimal individual peculiarities (individual immune fingerprints). On the other hand, abnormal metabolic changes which precede the clinical manifestation of different diseases showed easily detected changes, rather quantitative than qualitative, in the systems of natural autoantibodies in patients' sera (immunculus distortions). This phenomena could supposedly be used for "mapping" the state of physiological norm in terms of the millions of natural autoantibody repertoires, and for elaboration of the methods for early (preclinical) detection of potentially pathogenic metabolic changes. Could the individual features of the general network of constitutively expressed natural autoantibodies reflect the functional state of the body and be used for "mapping" of normal and pathological functional state? Could the changes in production of some biologically active natural autoantibodies not only reflect the state of the body, but be used for partial compensation of functional deficiency of certain molecular systems? These and related questions are discussed in this article. The research project "immunculus" is proposed for international cooperative investigations.

[Effect of antibiotic therapy on embryotropic antibody level in women]. / Vliianie antibiotikoterapii na coderzhanie émbriotropnykh antitel u zhenshchin.

Embriotropic antibodies (e-Ab) serum contents were analysed in 29 serum samples obtained from women suffering with primary lues. Before treatment the content of e-Ab against MBP, S100, ACBP14/18, and MP65 were markedly elevated in 28 samples. Two injections of Retarpen (2.5 mln Units with one week interval) were enough for effective treatment of lues. At the same time treatment caused deep and reversible inhibition of e-Ab production. One or two months later the levels of e-Ab returned to normal values in 21% of women, in 52% patients the hypoproduction, and in 27% the hyperproduction of e-Ab were noted. Deviations of e-Ab production after effective retarpen treatment suggest the existence of additional reasons which may influence e-Ab production, and necessity of additional diagnostic and curative measures for such women during pregravidal period.

[The humoral immunity characteristics of women with neurotic depressions]. / Osobennosti gumoral'nogo immuniteta u zhenshchin s nevroticheskimi depressiiami.

The levels of autoantibodies and their anti-idiotypes to proteins of nervous tissue (S100b, GFAP, MP65 and nerve growth factor) were studied in 85 women of 18-48 years of age with psychogenic neurotic depressions. It was found that the changes of the levels of autoantibodies to the proteins of nervous tissue correspond to various somatoautonomic manifestations and correlate with severity of depression, its typological variations and duration of the disease. The data obtained show a close relationship between nervous and immune systems that was expressed by some parallelism of the dynamics of the changes of both neurotic depressive symptoms and serum immunoreactivity to neuroantigens.

Serum anti-S100b, anti-GFAP and anti-NGF autoantibodies of IgG class in healthy persons and patients with mental and neurological disorders.

Natural autoantibodies of IgG class to proteins S100b, glial fibrillar acidic protein (GFAP), and nerve growth factor (NGF) are presented in serum of healthy adults and those levels/affinities are relatively constant and may vary among individuals within narrow limits. In patients with depressive disorder, epilepsy, multiple sclerosis, and Parkinson's disease dispersion of such autoantibodies serum levels were often found beyond the normal ranges. Most of the patient groups include cases with significantly elevated as well as abnormally decreased immunoreactivity parameters. This leads us to assumption that changes in some basic mechanisms of individual immune state represent the common features of different forms of pathology of the nervous system.

Possible mechanisms of diabetic fetopathy.

By using immunoaffine chromatography and ELISA it was found that 30-35% polyclonal of anti-insulin antibodies (AB1) in sera of diabetes patients has bound with high-affinity to Nerve Growth Factor (NGF). This indicates the presence of common epitop(s) in both molecules and could be a reason for NGF deprivation during formation of the nervous system in fetuses of diabetic pregnant women. Patient sera also usually characterized by elevated level of antiidiotypic antibodies (AIAb2) which interact with membrane insulin receptors, and may induce the general metabolic disturbances in fetus and newborns from diabetic mothers, fatal sometimes. High levels of anti-insulin/NGF Ab1 may bind excess of AIAb2 and prevents the insulin receptors dysfunction (typical for newborns in satisfactory health state). On the other hand--children with elevated levels of Ab1 at age 1-3 years often revealed clinical signs of neuropathology.

Changes of maternal serum natural antibodies of IgG class to proteins MBP, S100, ACBP14/18 and MP65 and embryonic misdevelopments in humans.

Immunoreactivity that is contents/affinity of natural antibodies (N-Ab) of IgG class to developmentally related proteins MBP, S100, ACBP14/18 and MP65 were measured in serum samples of 1987 women at their pregnancy terms of 3-12 weeks. The pregnancy results of the examined women were analyzed 4-9 months later. It was revealed that frequencies of cases of stopped early pregnancies, intrauterine and antenatal fetal deaths, and births of newborns with coarse inborn defects are directly related to deviation of the examined maternal N-Ab content/affinity from the physiological limits: abnormally high as well as abnormally low reactivity during first trimester of pregnancy, both could be related to unfavorable results of pregnancy.

[Antibodies against nerve tissue proteins S100, GFAP, and MP65 and pregnant women with early toxemia]. / Antitela k belkam nervnoi tkani S100, GFAP, MP65 u beremennykh s rannim toksikozom.

Serum levels/affinities of natural autoantibodies to proteins S100, GFAP and MP65 in patients with physiological pregnancy are usually constant and may vary among individuals within relatively narrow range. In patients with early toxicosis in pregnancy dispersion of serum autoantibodies levels were often found beyond the normal range. This group includes cases with significantly elevated as well as abnormally decreased immunoreactivity parameters. Percent of newborns with different deviations from women with abnormal serum levels/affinities of autoantibodies to proteins S100, GFAP and MP65 was higher 1,5-2 fold compared with population.

Transfer of elevated anti-S-100 autoimmunity from mother to offspring in rats.

Pregnant Wistar female rats were injected with polyclonal rabbit antibodies (AB) to S-100 brain protein. Control groups received equivalent amount of AB to bovine serum albumin or non-immune rabbit's IgG. An increased level of anti-S100 immunoreactivity was detected by ELISA or its enhanced variant ASPAG (from Amplified Solid Phase Attached Antigen-Antibody Grid formation) in the serum of 1 month old offsprings of group treated with AB to S-100. Obtained data indicate the possibility of inborn epigenetical "imprinting" of specific autoimmune reactions which may be important for the development of certain forms of nervous system diseases.

[Serum antibodies to brain protein antigens in cerebral palsy in children]. / Syvorotochnye antitela k belkovym antigenam mozga pri detskom tserebral'nom paraliche.

Using special brain antigen test-system ELITEST-24, ELISA assays of the serum of children with cerebral palsy were conducted. The data obtained were compared to relevant characteristics of the sera from neurologically and somatically healthy persons and patients with diagnoses of multiple sclerosis, schizophrenia, epilepsy and hepato-cerebral dystrophy according to special PC program VIZUAL and DIAGNOST. High specificity of the cerebral palsy anti-brain antigens reactivity was revealed by ELITEST technique. Moreover, the comparison of the mother-child pair immunoreactivity has been conducted. Evidence for hypothesis of epigenetically performing of children antibodies repertoires by mother-during-pregnancy immune status were obtained. Possible immunopathologic mechanisms of the disease are discussed.