Decreased Plasma Concentrations of the C4B Complement Protein 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).…”

“…Alternately, DR + activated T-lymphocytes were increased in blood of autistic patients in contrast to normal IL-2 receptors on lymphocytes, suggesting incomplete activation of the cells, often seen in autoimmune disease (Plioplys et al, 1994). DR + T-lymphocytes without the IL-2 receptor were also detected in autistic individuals, and the DR + T-lymphocytes were inversely correlated with a decreased plasma level of the C4B protein (Warren et al, 1994(Warren et al, , 1995. The B-lymphocyte antigen D8/17, with expanded expression in rheumatic fever, Sydenham's chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome with repetitive behaviors, was reported to be expressed to a greater degree in children with autism, and was correlated with the severity of repetitive behaviors (Hollander et al, 1999).…”

Immune Dysfunction in Tourette Syndrome

“…Reduced IgG3 synthesis may predispose TS patients to several types of infections, given that one of its main roles is to facilitate neutralisation and killing of microbes by activation of the complement cascade and activation of innate immune cells, such as NK cells [34]. Reduced IgA synthesis, if observed also at the level of IgA secreted by mucosae, might make mucosal surfaces more vulnerable to microbial colonisation; moreover, reduced IgA synthesis might disinhibit cellmediated immune responses and favour autoimmunity, as suggested by the high rate of autoimmune disorders in patients with IgA deficiency [33].…”

Autism as a disorder of neural information processing: directions for research and targets for therapy

“…In particular, an unusual number of people with autism may share all or part of the extended MHC haplotype B44-SC30-DR4 [253,78,252,232]. Evidence also exists for a link between autism and a null allele of the C4B gene, in the class III MHC region, [254], and correspondingly low levels of C4b protein [249] which is essential in activation of the classical complement pathway. The previously mentioned possible involvement of the UBE3A gene also ties into MHC functioning, since the peptide fragments presented by MHC molecules can be produced by the proteolytic activity of ubiquitin ligase.…”