EVALUATION OF MARKERS OF INFLAMMATION AND NEURONAL DAMAGE IN PATIENTS WITH AUTISM SPECTRUM DISORDERS ASSOCIATED WITH GENETIC DEFICIENCY OF THE FOLATE CYCLE
Backgrounds. The evidence base of the association of genetic folate cycle deficiency (GFCD) and autism spectrum disorders (ASD) in children is based on
the results of 5 meta-analyzes of randomized controlled clinical trials. Systemic inflammation, which occurs as a result of GFCD in children with ASD, is considered an important mechanism for the development of encephalopathy.
The clinical significance of the phenomenon of persistent systemic inflammation in children with ASD needs to be clarified. It is advisable to study the relationship between increased serum concentrations of certain pro-inflammatory mediators and indicators of neuronal damage in such cases.
The aim: to study the serum concentrations of typical proinflammatory mediators tumor necrosis factor alpha (TNF-alpha), interleukin IL-6 (IL-6) and tumor- M2-pyruvate kinase (TM2PK) in children with ASD associated with GFCD, with clarification of their with serum concentrations of so-called markers of neuronal
damage CNS neuron-specific enolase (NSE) and S-100 protein to expand the understanding of the influence of systemic inflammatory response on the development of encephalopathy in this pathology and the discovery of new points of application of neuroprotective treatment.
Materials and methods. The study group (SG) consisted of 138 children diagnosed with autism spectrum disorders (DSM-IV-TR and ICD-10), who had a genetic
deficiency of the folate cycle (MTHFR C677T + MTHFR A1298C and/or MTR A2756G and/or MTRR A66G). The control group (CG) included 51 healthy children of the appropriate age and gender distribution.Serum concentrations of pro-inflammatory mediators TM2PK, TNF-alpha, IL-6 and neuronal damage indicators
NSE and S-100 protein were studied.
Research results and their discussion. There was an increase in serum concentrations of TM2PC in 119 of 138 patients with SG (86%) and only in 11 of 51 children CG (22%) (p<0.05; Z<Z0.05), TNF-alpha – in 85 of 138 children SG (62%) and only 7 of 51 children CG (14%) (p<0.05; Z<Z0.05), IL-6 – 43 of 138 children
SG (31%) and only 3 of 51 children of CG (6% of cases) (p<0.05; Z<Z0.05). The average serum concentrations of TM2PC in SG was 63.1±3.74 IU/ml compared with 23.2±0.91 IU/ml in CG (p<0.05; Z<Z0.05), TNF-alpha – 13,7±0.65 pg/ml compared with 5.3±0.38 pg/ml in CG (p<0.05; Z<Z0.05), IL-6 – 8.7±0.57 pg/ml compared with 3.6±0.27 pg/ml in CG (p<0.05; Z<Z0.05). TM2PK, TNF-alpha and IL-6 differed significantly in sensitivity, lability and specificity as markers of systemic inflammation in children with ASD associated with GFCD.
All three studied indicators of systemic inflammation were associated with an increase in serum concentrations of laboratory indicators of neuronal damage NSE and S-100 protein, indicating the link between systemic inflammatory response and the development of encephalopathy in children with ASD associated with GFCD.
Conclusions. The obtained data not only expand modern ideas about the development of systemic inflammation and its participation in the formation of encephalopathy in children with ASD associated with GFCD, but also open the way for testing modern anti-inflammatory neuroprotective treatment strategies.
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