TH1/Treg ratio may be a marker of autism in children with immune dysfunction

Abstract

Evidence suggests a link between autism spectrum disorder (ASD), behavioral symptoms in the context of ASD, and presence of an altered immune function. Several studies have highlighted differences in T-lymphocyte subpopulations, their activation status, and their response to stim-ulation in children and adults with ASD. These T cell abnormalities have often been associated with more impaired behaviors. However, few studies have attempted to address whether T cell subsets have the potential to serve as biomarkers in ASD. Moreover, although many studies have been performed in Western populations, few (if any) have been performed in Asian populations in mainland China. In this study we used intracellular cytokine flow cytometry to assess the fre-quencies of CD4+ T-cell subpopulations (T-helper (TH) 1, TH2, TH17, Foxp3+ regulatory T cells (Treg) as well as CD8+, subpopulations of T cytotoxic (TC) 1, TC2, and TC17 in 82 children with ASD and 50 healthy typical developing children from the Second Affiliated Hospital of Kunming Medical University of Yunnan province. To further elucidate immune status cytokine levels were also measured in the plasma and serum using a bead-based cytokine assay. Our results showed that the frequency of circulating Treg cells and the levels of active TGF-beta 1 in plasma were lower in children with ASD than in healthy controls. In contrast, the frequencies of TH1, TH2, TH17 and TC1 cells were increased. Proinflammatory cytokine levels of TNF-alpha, IL-4, IL-5 and IL-17A were higher in the plasma of children with ASD compared to typical controls. We also found an as-sociation between the severity of behavior impairments in ASD children and altered immune responses as measured using the effector T cell responses and regulatory responses (using Teff/Treg ratios). Higher the Teff/Treg ratios, were associated with more severe problematic behavioral symptoms. Further, the potential biomarker relevance of Teff/Treg ratio was evaluated by the receiver operating characteristics curve. Data suggests that high TH1/Treg cell ratios could also be used as a potential marker for the diagnosis of children with ASD. Overall, our data suggest an imbalance in inflammatory and regulatory immune responses in ASD. Ratios of inflammatory/ regulatory cells or cell frequencies such as Teff/Treg cells may be useful biomarkers for children with ASD with immune dysfunction.