**7. Non-infection causes of immune deviations in women of fertile ages**

with external marker signs of HPV infection (warts, condylomas with any location).

Bacterial and/or viral infection (acute as well as activation of opportunistic infection) probably is the most often reason of deviations in activity of the immune system of investigated person, monitored by changes in serum content of natural autoantibodies. However other reasons conditioned the long-term immune deviations negatively influencing upon general fertility state, conception, pregnancy course and fetal development may be also important. Tight functional interrelation and prominent mutual influences the immune and neuro-endocrine systems [Poletaev et al., 2002] provides effect of falling dominoes. Any changes in the nervous system or endocrine system will obligatory lead to functional changes in the immune system. For example stroke, or thyroidal pathology, or hypothalamic dysfunction, etc. will be accompanied by changes in production and serum content plurality of autoantibodies, sometimes prominent and long-lasting [Poletaev, 2010]. In this connection even chronic psychogenic stresses may became the reason for immune deviations, negatively influencing upon fertility state [Poletaev, 2010]. Corresponding cases may be effectively treated by specialist in psychotherapy with or without using of antidepressants or similar medicine. Different ecological pollutants also can influence upon the immune state and, mediately, the fertility of investigated patient. The same situation may be provoked by incompetent medication in a course of non-professional "selftreatment". All above mentioned factors indicate for necessity of careful analysis of patient anamnesis: clarification of the main reason(s) leading to immune deviations in observed woman may become the first step in correction of reproductive dysfunction in each individual case. the of

#### **8. Maternal immune imprinting**

The biological meaning of a maternal organism in the development of a fetus is exclusive and maternal influences upon child's phenotype, have a priority compared to the paternal ones. It is illustrated clearly by the phenomenon of the epigenetic maternal immune imprinting of a system: Mother–Fetus–Child. The essence of this phenomenon is the "inheritance" by the child's organism many of the individual traits of the immune state of the mother, but not the father [Poletaev, 2008]. As a result, specific features of a child's immunity/autoimmunity become more or less an accurate copy (imprint) of the maternal immune state.

The adaptive meaning of maternal immune imprinting is evident. This phenomenon is responsible for the resistance acquisition against infection diseases by any newborn before the first real contact with the widespread viruses and bacteria. A more pronounced antiinfection immunity in the mother provides more potent inborn resistance against the same infection in her child [Lemke & Landor, 1999]. Observations of such kind provide the

Maternal Immunity, Pregnancy and Child's Health 51

Especially if predictive diagnosis was combined with treatment, run over under control of immune parameters. It should be noted - in opposite to genetic aberrations, the immune

Soon after Chernobyl disaster the specialized immunochemical methods for mass-scale investigation of the general health state as well as reproductive health state inhabitants of polluted areas were worked out in the former Soviet Union. These methods were generally named as ELI-Tests (from: **E**nzyme-**L**inked-**I**mmune-**Tests)**. One of these methods, just method ELI-P-Complex (abbreviation "**P**" – from Pathology in Pregnancy) was intended for preventive investigations of a fertile age women. Since 1994 the method ELI-P-Complex has been used successfully for prognosis of the development of planned pregnancy in general obstetrician practice in Russia. Method is intended for analysis of individual "profiles" (patterns) of twelve autoantibodies of IgG class in the sample of blood serum. It is based upon evaluation of partial changes in the contents of autoantibodies against choriogonadotropin, ds-DNA, β2-Glycoprotein I, collagen II type, Fc-fragment of IgG, insulin, thyroglobulin, S100, Spr-06, ANCA, TrM-03, and KiM-05 [Poletaev, 2010]. In spite of diagnostic and prognostic effectiveness of the method proved in thousands investigations, the detailed mechanisms mediating influence of immune deviations measured by ELI-P-Complex upon the gestation process should be elucidated. Nevertheless, there is basis for some propositions. For example, any long-lasting active infection process (viral or bacterial) may be etiologically related to antiphospholipid syndrome induction and accompanied, in particular, by abnormally elevated serum levels of autoantibodies against β2-Glycoprotein I and DNA [Poletaev, 2008]. The mentioned autoantibodies could be pathogenically related to changes in blood coagulation [Sherer & Shoenfeld, 2004] which, in turn, may cause vascular problems in placenta and affect the gestation process. Relative surplus of anti-collagen II autoantibodies may indicate inborn or acquired defects of the connective tissue and active adhesion process. Changes in serum autoantibodies against S100 are typical for some women with still-births and fetal/newborns neural malformations in anamnesis, and are related in most cases with active replicated papilloma viruses. A surplus of autoantibodies against choriogonadotropin may be the reason for deficiency in this hormone, which is important for placenta development and maturation, as well as for cases of premature ovarian failure [Tuohy & Altuntas, 2007]. Excess of autoantibodies against Fc-fragments of IgG (Rheumatoid factor) is indicator of inflammatory processes of any localization. Elevated peak of autoantibodies against Spr-0.6 may be indication of declining fertility and in most cases is sensitive marker sign of endometritis and/or inflammatory processes in other pelvic organs. Abnormal rise of autoantibodies against insulin, thyroglobulin, ANCA, TrM-03, and KiM-05 in detected profiles may be markers of diabetic fetopathy, thyroidal abnormalities, vasculopathy and kidney-related disorders in pregnant women [Poletaev, 2010]. An early detection (especially before planned pregnancy) of relative deviations in serum content some of measured autoantibodies is especially important for revealing of individuals with elevated risk of abnormalities expected

deviations may be effectively treated in the most cases.

at pregnancy and implementation of necessary prophylactic measures.

The main field for using of ELI-P-Complex method is screening of women planning their pregnancy, IVF including. Immune deviations revealed by this method are related to or reflect some individual health problems, and characteristic changes of autoantibodies profiles, that

**10. Clinical illustrations** 

ground for possible induction of the inborn resistance to infectious diseases in a child after an active immunization of the mother before her pregnancy. If such approaches will be introduced in medical practice, it should help to reject certain vaccinations or at least decrease their number and frequency for the babies [Poletaev, 2010].

Unfortunately, the Nature is lack of perfectness, and there is another (negative) side of the coin. If mother has been suffered from any kind of immune deviations, the undesirable effects can be produced upon her child directly, as well as indirectly by mechanism of maternal immune imprinting. For example systemic lupus erythematosus in the mother may lead to the development of newborn's lupus in babies at 4-8 months of the postnatal life [Poletaev, 2008]. Woman with abnormally elevated production of autoantibodies against insulin and/or insulin receptors can "imprint" these features in the immune state of her child. As a result, an abnormally elevated production of the same Autoantibodies may be revealed in a 4-6 years old child, and may become a risk factor for the early development of the diabetes mellitus [Budykina, 1998]. The elevated production of anti-thyroid autoantibodies may be revealed for years in children, whose mothers had thyroid problems, and may become the risk factor for the thyroid gland diseases in child [Poletaev, 2008]. Elevated rates of the same forms of pathology in children (endocrine, cordial, nephrological, etc.) which was presented in mothers during pregnancy course [Khlystova, 1987] may be directly related to the phenomenon of maternal immune imprinting.

The main mechanisms of the maternal immune imprinting remain obscure although, we can propose that the fact of antigenic specificity of the phenomenon implies the participation of specialized autoantibodies (probably anti-idiotypic autoantibodies) and/or AG-specific lymphocytes. Transferred trans-placentally maternal anti-idiotypic autoantibodies and/or memory lymphocytes can be the basic elements, which provide a specific activation and tuning of certain clones of the fetal T- and B-lymphocytes, and become main triggers of the inborn pre-formation of the Immunculus of the fetus-newborn-child (similar to maternal ones).

Future investigations of the maternal immune imprinting may provide the new approaches in prediction and treatment of a large group of inborn abnormalities. Besides, the comprehension of the phenomenon may serve as an impetus for the promotion of the fundamental research in the fields of maternal-fetal interactions.
