THE PROBLEM OF AUTISM SPECTRUM DISORDERS ASSOCIATED WITH THE GENETIC DEFICIENCY OF THE FOLATE CYCLE AS A MANIFESTATION OF THE IMMUNODEFICIENCY DISEASE
Keywords:
autism, folate cycle, NK-, NKT-cells, immunodeficiencyAbstract
Formulation of the problem. Recently, more researchers have pointed out the association of autistic spectrum disorders, associated with primary folate deficiency, with immune-related pathology. Analysis of recent research and publications. The sources of scientific literature describe various forms of primary immunodeficiency disorders in autistic spectrum disorders, and studies on some primary immune dysfunctions indicate an increased risk of developing autism. Target formulation: To conduct a comprehensive assessment of the immune status in children with autism spectrum disorders associated with a genetically determined folate cycle deficiency. The presentation of the main material. As a result of assessing the immune status, it was found that almost all children with a genetic deficiency in the folate cycle were immunocompromised individuals. The basis of the identified immunodeficiency was a sharply reduced number of cells of lymphocyte subpopulations with the phenotype CD3 – CD16 + CD56 +, called natural killers (natural killers, NK), and the phenotype CD3 + CD16 + CD56 +, or natural killer T cells (natural killer T-cell, NKT) in peripheral blood. In addition, other disorders of the immune status were much less common among children with autistic spectrum: a decrease in the number of CD8 + T-lymphocytes (23%), CD4 + T-cells (12%), CD19 + B-lymphocytes (9% of cases). Disimmunoglobulinemia, including isolated and combined deficiencies of classes and subclasses of immunoglobulins, was detected in 43% of cases, but more often it was shallow and was transient in nature. Hypoimmunoglobulinemia is registered only in 17% of cases. Phagocytic myeloperoxidase deficiency was noted in 35% of cases and was combined with disturbances in other parts of the immune system in a variable manner. Since the immune deficiency in children with autism spectrum disorders was dominated by cellular immunity disorders, the existing infectious syndrome was represented mainly by intracellular pathogens, the majority - opportunistic viruses from. family herpes. There was an increased production of anti-brain antibodies, mainly against the myelin basic protein and neuron-specific enolase (about 70%), as well as signs of autosensitization of neutrophils (32%) and CD8 + cytotoxic T-lymphocytes (24% of cases) to brain antigens. Signs of anti-myelin autoimmunity correlated with radiological manifestations of leukoencephalopathy. Among the manifestations of anti-neuronal autoimmunity, the production of autoantibodies to glutamine decarboxylase neurons (GADA) was most often detected - in 61% of cases, less often - to potassium channels of nerve cells (34% of cases). Some patients had autoimmunization to amphiphysin (19%) and receptors for N-methyl- D-aspartate (NMDA) (3%). Conclusions and prospects for further research. Immune dysfunction in autism spectrum disorders has a variable immunological phenotype, however, deficiencies of NK-, NKT-cells, CD8 + T-lymphocytes and myeloperoxidase are the most typical signs of the disease. Apparently, this is a new form of primary immunodeficiency, requiring further study.
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