AUTHOR=Harville Terry , Rhodes-Clark Bobbie , Bennuri Sirish C. , Delhey Leanna , Slattery John , Tippett Marie , Wynne Rebecca , Rose Shannon , Kahler Stephen , Frye Richard E. TITLE=Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD) JOURNAL=Frontiers in Psychiatry VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00612 DOI=10.3389/fpsyt.2019.00612 ISSN=1664-0640 ABSTRACT=

Autism spectrum disorder (ASD) is a behaviorally defined disorder that is now thought to affect approximately 1 in 69 children in the United States. In most cases, the etiology is unknown, but several studies point to the interaction of genetic predisposition with environmental factors. The immune system is thought to have a causative role in ASD, and specific studies have implicated T lymphocytes, monocytes, natural killer (NK) cells, and certain cytokines. The human leukocyte antigen (HLA) system is involved in the underlying process for shaping an individual’s immune system, and specific HLA alleles are associated with specific diseases as risk factors. In this study, we determine whether a specific HLA allele was associated with ASD in a large cohort of patients with ASD. Identifying such an association could help in the identification of immune system components which may have a causative role in specific cohorts of patients with ASD who share similar specific clinical features. Specimens from 143 patients with ASD were analyzed with respect to race and ethnicity. Overall, HLA-Cw7 was present in a much greater frequency than expected in individuals with ASD as compared to the general population. Further, the cohort of patients who express HLA-Cw7 shares specific immune system/inflammatory clinical features including being more likely to have allergies, food intolerances, and chronic sinusitis as compared to those with ASD who did not express HLA-Cw7. HLA-Cw7 has a role in stimulating NK cells. Thus, this finding may indicate that chronic over-activation of NK cells may have a role in the manifestation of ASD in a cohort of patients with increased immune system/inflammatory features.