Increased frequency of the null allele at the complement C4b locus in autism

Abstract

SUMMARYAssociations between C4 deficiency and autoimmune disorders have been found over the past several years. Since autism has several autoimmune features, the frequencies of null (no protein produced) alleles at the C4A and C4B loci were studied in 19 subjects with autism and their family members. The autistic subjects and their mothers had significantly increased phenotypic frequencies of the C4B null allele (58% in both the autistic subjects and mothers, compared with 27% in control subjects). The siblings of the autistic subjects also had an increased frequency of the C4B null allele, but this increase was not significant. The fathers had normal frequencies of this null allele. All family members had normal frequencies of the C4A null allele, all normal C4A and C4B alleles and all BF and C2 alleles.

Theoretical aspects of autism: biomarkers—a review

“…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). The C4B protein is essential in the activation of the classical complement pathway that results in lysis (Kunkel et al, 1985).…”

Immune Dysfunction in Autism Spectrum Disorder

“…Previous research in our laboratory utilizing a protein immunoelectrophoresis assay demonstrated a significant link to a deficiency of C4B protein and autism (Warren et al, 1991). It was reported that a C4B null allele (C4B gene deletion) was significantly more common in subjects with autism than in subjects without autism.…”

“…However, there may be genes that are being missed, as there are close to 100 genes in this region. Research in our laboratory has noted differences in certain HLA class I and class II alleles as well as C4 complement genes in the class III region (Torres et al, 2002;Torres et al, 2006;Warren et al, 1991;Warren et al, 1996).…”

“…In addition to single genes and alleles, several publications have shown haplotypes to be associated with autism (Table 1). Warren et al (1991) first reported that the AH 44.1-SC30-DR4 was associated with autism with a relative risk of 7.9. That result was confirmed in a new case/control population (Daniels et al, 1995).…”

Beta-2-Microglobulin in Autism Spectrum Disorders

“…Issues such as increased inflammation in the brain [5,6] , autoantibodies to brain tissues (reviewed in [4,[7][8][9][10][11] ) and maternal/perinatal infections ( [12,13] , reviewed in [14] ) have been associated with the development of ASD. Immune system related genes have also been linked to ASD, including the complement component C4B gene and the extended HLA haplotype B44-S30-DR4 ( [15][16] ). Due to the extensive crosstalk between the immune system and central nervous system (CNS) during development and beyond [17][18][19] , it is conceivable that aberrant immune activity could be detrimental to CNS function.…”