Adaptive maternal immune deviations as a ground for autism spectrum disorders development in children.

Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 - 1:150) with late diagnosed autism spectrum disorders (ASD) and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet. One of the most likely mechanisms inducing ASD may be a maternal immune imprinting. This phenomenon is based on transplacental translocation of maternal antibodies of IgG class and, as a consequence, on the epigenetic "tuning" of immune system of the fetus and child. This mechanism provides development of child's anti-infection resistance before meeting with microorganisms, but it can be also a cause of inborn pathology including the ASD appearance. The quantitative changes in maternal blood serum autoantibodies depend on a specific microbial population, or are induced by environmental chemical pollutants in association with some individual features of the maternal metabolism. These immune changes are adaptive in most cases for the maternal organism, but can be pathogenic for the fetus in some cases. We discuss in the present paper the possibilities to predict the risk from abnormal development of nervous system in fetus and early diagnosis of ASD in high-risk group of children.

Integrating immunity: the immunculus and self-reactivity.

The most important theoretical contribution to autoimmunity was the clonal selection theory of Burnet. This thesis, including the unique terminology of the forbidden clone, laid the foundation for discussions and research regarding self-reactivity and remains the foundation for discussions of thymic education. There were, however, additional works which suggested that autoantibodies, coined natural autoantibodies, exist even in healthy individuals. The ontogenic appearance of the immune system was a series of events that were developed in evolution to recognize the biologic essence of complementary antigen recognition and elimination of foreign pathogens. Interestingly, microbial and host epitopes are often highly conserved in evolution and this homology has functional significance for both the microbe and the host. Further, while the immune system is a series of interconnecting pathways, in reality it is also composed of promiscuous and sometimes independent pathways. The interaction between antibodies and epitopes is determined not necessarily by a primary chemical structure, but more likely by the stereochemistry of the antigen. As such, we increasingly recognize a large repertoire of natural autoantibodies and the development of autoimmune disease requires more than an innocent bystander mimicry pathway, but rather expansion of lymphocytic populations that are either already naturally present, or derived from genetic/acquired defects in immune regulation. We suggest that discussion of loss of tolerance should not include focus on the classic terminology of peripheral versus central tolerance but must consider the integrative activity of the immune system and the balance between well-balanced self-reactivity and the processing of foreign antigens. These events, while primarily theoretical, provide a framework to understand the elements involved in genetic susceptibility to autoimmunity.

Application of ELI-P-complex method in clinical obstetrics.

PROBLEM: Evaluation of embryotropic natural auto-antibodies (a-Abs) of IgG class in blood serum of women planning pregnancy or in that of already pregnant women is necessary in order to predict the course of gestation and pregnancy outcomes. METHOD OF STUDY: The ELISA-based probability of pathology in pregnancy (ELI-P)-complex method is based on the enzyme-linked immunosorbent assay technology. We used it to evaluate serum samples of 380 women with complicated obstetric anamnesis (COA) by measuring contents/affinity (immunoreactivity; IR) of a-Abs interacting with eight specific antigens related to mechanisms of gestation process. The control group was presented by 30 healthy women without COA. For each woman we carried out a pre-gestational investigation and, if necessary, performed a standard antibacterial/antiviral treatment and correction of endocrine state. RESULTS: We found that 92.6% of investigated women with COA were characterized by deviations in serum IR of the examined a-Abs. In contrast, in the control group there were no immune deviations related to the examined a-Abs. A direct relation was revealed between normal or deviated serum IR of investigated a-Abs and physiological or pathological pregnancy development and pregnancy outcome. CONCLUSION: We recommend ELI-P-complex as a screening and monitoring tool for predicting pregnancy outcomes and providing proper treatment therapies.