Dysregulation of the expression of HLA-DR, costimulatory molecule, and chemokine receptors on immune cells in children with autism

Abstract

Autism spectrum disorder (ASD) is a heterogeneous disorder diagnosed based on the severity of abnormalities in social skills. Several studies have acknowledged the presence of abnormal immune functions among individuals diagnosed with ASD. HLA-DR (human leukocyte antigen-antigen D related) has been shown to play a significant role in several inflammatory and neurological disorders; however, the role of HLA-DR signaling in ASD has not yet been fully clarified. In this study, we investigated the role of HLA-DR signaling in children with ASD. Flow cytometric analysis, using peripheral blood mononuclear cells (PBMCs), revealed the numbers of CD4⁺, CD8⁺, CD28⁺, CXCR4⁺, and CCR7⁺ expressing HLA-DR cells in typically developing (TD) controls and children with ASD. We also determined the numbers of IFN-γ⁺, IL-21⁺, and Foxp3⁺ expressing HLA-DR cells in TD controls and in children with ASD using PBMCs. We observed mRNA and protein expression levels of HLA-DR by RT-PCR and western blotting analysis. Our results revealed that children with ASD had significantly increased numbers of HLA-DR⁺CD4⁺, HLA-DR⁺CD8⁺, CD28⁺HLA-DR⁺, HLA-DR⁺CXCR4⁺, HLA-DR⁺CCR7⁺ cells compared with TD controls. We found that children with ASD showed increased HLA-DR⁺IFN-γ⁺ and HLA-DR⁺IL-21⁺ and decreased HLA-DR⁺Foxp3⁺ expression levels compared with TD controls. Furthermore, children with ASD showed higher HLA-DR mRNA and protein expression levels compared with TD controls. These results indicated that HLA-DR could play an essential role in the immune abnormalities associated with ASD.

Keywords: Autism spectrum disorder; Cytokines; HLA-DR; Peripheral blood mononuclear cells; Transcription factors; Typically developing controls.