• Dmytro Maltsev Experimental and Clinical Medicine Institute at the O.O. Bohomolets National Medical University
Keywords: natural killers, natural killer T cells, cytotoxic T lymphocytes, myeloperoxidase, homocysteine


Introduction. The results of the last 5 meta-analyzes of randomized controlled clinical trials indicate an association of genetically determined deficiency of folate cycle enzymes (GDFC) and autism spectrum disorders (ASD) in children. There have been reports of an association of ASD with immunodeficiency disease and signs of immune dysregulation, as well as immunedependent mechanisms of CNS damage in children with ASD.

The aim of the study: to conduct a comprehensive analysis of immune status in children with ASD associated with GDFC, due to specific biochemical disorders and immune-dependent clinical manifestations.

Materials and methods. Medical data of 225 children aged 2 to 9 years with GDFC, in which clinical manifestations of ASD (183 boys and 42 girls) were noted, were retrospectively analyzed. The diagnosis of PAS was made by child psychiatrists according to the criteria of DSM-IV-TR (Diagnostic and Statistical Manual of mental disorders) and ICD-10 (The International Statistical Classification of Diseases and Related Health Problems) (study group; SG). The control group (CG) included 51 mentally healthy children (37 boys and 14
girls) of similar age distribution, who did not suffer from GDFC and ASD.
Pathogenic polymorphic variants of folate cycle genes were determined by restriction PCR (Sinevo, Ukraine).
Immunological examination included the study of the subpopulation composition of lymphocytes using laser flow cytofluorimetry (cytofluorimeter Epics Xl, USA) and the method of indirect immunofluorescence with monoclonal antibodies to CD-markers with two or three CD (CD19+CD3-, CD3+CD4+, CD3+ CD8+, CD3—CD16+CD56+, CD3+CD16+CD56+) (Beckman Coulter reagents, USA). Phagocytosis was assessed by the activity of myeloperoxidase (flow cytofluorimetry) and NADP oxidase (HCT test). Serum concentrations of immunoglobulins
of the main classes (M, G, A) were determined by the results of solid-phase ELISA. The concentration of IgE, IgD and IgG subclasses (IgG1, IgG2, IgG3, IgG4) in serum was measured by solid-phase ELISA (VectorBEST, RF; MDI Limbach Berlin GmbH, Germany).
To determine the probability of differences between indicators in the observation groups used Student’s parametric T-test with a confidence probability p and non-parametric criterion – the number of Z signs according to Urbach Yu.V. To study the associations between the studied indicators, the odds ratio (OR) and the 95% confidence interval (95% SI) were used.
The research was performed as a fragment of research work commissioned by the Ministry of Health of Ukraine (ж state registration 0121U107940).

Results and discussion. Deficiency of NK cells was observed in 65%, NKT cells – in 73%, CD8+ cytotoxic Tlymphocytes – in 49%, myeloperoxidase – in 39%, and dysimmunoglobulinemia – in 37% of cases among patients with SG (p<0,05; Z<Z0.05). The association of the main immunological disorders (deficiencies of NK-, NKTcells, cytotoxic T-lymphocytes, myeloperoxidase) and biochemical disorders in GDFC – hyperhomocysteinemia, deficiencies of vitamins B6, B12, D3, folic acid and signs of mitochondrial dysfunction is shown. The association of identified immune dysfunction with immune-dependent clinical manifestations has also been demonstrated.

Conclusions. The obtained data allow us to identify a new primary immunodeficiency – immunodeficiency associated with GDFC.


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How to Cite
Maltsev, D. (2022). РЕЗУЛЬТАТИ ОЦІНКИ ІМУННОГО СТАТУСУ У ДІТЕЙ З РАС: ІМУНОДЕФІЦИТ, АСОЦІЙОВАНИЙ З ГЕНЕТИЧНИМ ДЕФІЦИТОМ ФОЛАТНОГО ЦИКЛУ. Immunology and Allergy: Science and Practice, (4), 5-22. https://doi.org/10.37321/immunology.2021.4-01