DR-Positive T Cells in Autism: Association with Decreased Plasma Levels of the Complement C4B Protein

Abstract

Autism is a developmental disorder characterized by severe communication, social and behavioral abnormalities. Over the past several years a fair amount of evidence has accumulated suggesting that some cases of autism may be associated with immune abnormalities and with products of the HLA complex including the C4B gene located in the class III region of HLA. This study sought additional evidence for an association of autoimmune processes with autism by investigating the presence of activated T cells in 26 autistic subjects. Fourteen of the autistic subjects had DR+ T cells, an indicator of activated T cells, but none of the autistic subjects had T cells expressing the interleukin-2 receptor, another indicator of T cell activation. Similar findings of incomplete or partial T cell activation have been reported in autoimmune disorders and in a recent study of autism. In the current investigation, the DR+ T cells were not found to be associated with age of the autistic patients but were inversely correlated with a decreased plasma level of the C4B protein. In conclusion, this study provides additional evidence for the involvement of an autoimmune mechanism in autism.

Theoretical aspects of autism: biomarkers—a review

“…C4B complement protein was found to be deficient in the blood of autistic patients (Warren et al, 1994(Warren et al, , 1995. This finding correlates with studies that indicate the complement C4B gene null allele (i.e., the missing or nonfunctional C4B gene) is more frequent in individuals with autism Warren et al, 1991).…”

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

“…18,19 Among the genes implicated in autism, several relate to immune regulation and function, including HLA-antigen presentation molecules and components of the complement system. 14,[20][21][22][23][24][25][26][27] Although abnormalities of cytokines and chemokines have been reported in the blood of patients with autism including plasma levels of tumor necrosis factor-a (TNF)-a, TNF receptor II, Interferon-gamma (IFNg), Interleukin-12 (IL-12), and IL-10, no definitive profile has emerged. Indeed, the changes reported in cytokine levels may occur in separate subgroups of autism subjects that have different clinical phenotypes.…”

Neurotoxic effects of postnatal thimerosal are mouse strain dependent

“…7,8 A large, retrospective study investigating the association of thimerosal-containing vaccines and neurodevelopmental outcomes in an unselected cohort was inconclusive and called for further research into vulnerability factors. 9 An autoimmune diathesis is described in ASD probands [10][11][12][13][14][15] and their first degree relatives. 16,17 Major histocompatibility complex (MHC) genes regulate risk of mercury-induced autoimmunity in mice.…”