Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism

Abstract

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.

Keywords: adaptive behaviour; antibodies; autism spectrum disorders; human endogenous retroviruses; immune response.

Figure 1

Heatmap displaying the r values obtained from Spearman’s correlation analysis performed among HERV-H-, HERV-W- and HERV-K-derived epitopes in ASD children (A) and in HC children (B).

Figure 2

Linear regression between HERVs antibody levels and age of all participants (children and mothers). (a) shows the linear regression between anti-HERV-H and age; (b) shows the linear regression between anti-HERV-K and age; (c) shows the linear regression between anti-HERV-W and age.95% CI, confidence interval fixed at 95%. Statistical significant levels fixed at * p < 0.05.

Figure 3

ELISA-based analysis of antibody presence against HERV-H-, HERV-W- and HERV-K-derived epitopes. Plasma samples from ASD and HCs populations were tested against HERV-H (229–241) (A,D), HERV-W (248–262) (B,E) and HERV-K (19–37) (C,F). Scatter plots represent median with 95% of CI. The Mann–Whitney p-value is indicated in the upper part of each graph.

Figure 4

Caption title. Scatter plots of the Pearson’s correlation test between the ABAS-II questionnaire—GAC (Global Adaptative Composite)—Score and the anti-HERVs levels in children with ASD. (a) Association between anti-HERV-K and the Global Adaptive Composite Score of the ABAS-II questionnaire in children with ASD diagnosis. (b) Association between anti-HERV-H and the Global Adaptive Composite Score of the ABAS-II questionnaire in children with ASD diagnosis. (c) Association between anti-HERV-W and the Global Adaptive Composite Score of the ABAS-II questionnaire in children with ASD diagnosis. Statistical significant levels fixed at * p < 0.05.