• Дмитро Мальцев Experimental and Clinical Medicine Institute at the O.O. Bohomolets National Medical University
Keywords: immunodeficiency, immunodiagnostics, antimicrobial therapy, immunotherapy, microbiota- gut-brain axis


Backgrounds. The results of five meta-analyzes of randomized controlled clinical trials suggest an association of genetic folate cycle deficiency (GDFD) with autism spectrum disorders (ASD) in children. In such cases, immunodeficiency and immune dysregulation are formed, which reduces resistance to some microorganisms.
The aim of the study: to study the structure of the microbial spectrum in children with ASD associated with GDFC according to the accumulated evidence base and to evaluate the association of detected microorganisms with indicators of immune status to improve understanding of pathogenesis of encephalopathy and algorithms for diagnostics, monitoring and treatment.
Materials and methods. Medical data of 225 children aged 2 to 9 years with GDFC, in which clinical manifestations of ASD were observed (study group; SG; 183 boys and 42 girls) were retrospectively analyzed. The control group (CG) included 51 clinically healthy children (37 boys and 14 girls) of similar age and gender distribution who did not suffer from GDFC. A special laboratory examination of children in the observation groups was performed taking into account current data about the microbial spectrum in patients with ASD according to publications in PubMed and Embase. To study the associations between the 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 (№ state registration 0121U107940).
Results and discussion. TTV was observed in 87%, HHV-7 – 79%, HHV-6 – 68%, EBV – 59%, Streptococcus pyogenes – 46%, Candida albicans – 41%, Borrelia – 34%, Mycoplasma pneumoniae – 27%, Chlamydia pneumoniae – 26%, Yersinia enterocolitica – 23%, Toxoplasma gondii – 19%, congenital CMV neuroinfection – 7%, the consequences of HSV-1/2-neuroinfection – 5% of cases in SG (p<0,05; Z<Z0,05). HHV-6, HHV-7 and EBV have been associated with NK-, NKT- and CD8+ cytotoxic T-lymphocyte deficiencies. TTV was also associated with NK- and NKT-lymphocyte deficiencies, but not with deficiency of CD8+ cytotoxic T cells. Streptococcal infection has been associated with hypo- and dysimmunoglobulinemia, as well as myeloperoxidase deficiency. Candidiasis was associated only with myeloperoxidase deficiency. Toxoplasmosis has been reported in CD4+ T-helper deficiency and combined immune disorders. The consequences of congenital CMV neuroinfection have occurred only in combined immune disorders.
Conclusions. Children with ASD associated with GDFC are characterized by a specific microbial spectrum with predominance of intracellular opportunistic and conditionally pathogenic pathogens, which is determined by the disorders of immune status provoked by GDPC, which should determine the algorithm of rational antimobiological, immunological diagnostic search and treatment.


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