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

Department of Biology, Utah State University, Logan 84322-6800.
Clinical & Experimental Immunology (Impact Factor: 3.04). 04/1991; 83(3):438-40. DOI: 10.1111/j.1365-2249.1991.tb05657.x
Source: PubMed


Associations 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.

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Available from: Dennis Odell, Oct 02, 2015
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    • "The A*02-B*44 haplotype is part of the larger B44-SC30-DR4 extended haplotype, which is more frequent in autistic children than in controls [14, 20]. This extended haplotype also contains two genetic loci previously shown to be associated with autism, the C4B null allele, and HLA-DR4 [15, 21, 39]. "
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    ABSTRACT: Earlier reports showed the relationship between autism and immune genes located in the human leukocyte antigen (HLA). In this current study, we compared the HLA class I and class II alleles and haplotypes in 35 autistic children with 100 control subjects from Saudi Arabia, using PCR-SSP method and Luminex technology. In class I the HLA-A*01 (P = 0.03, OR 2.68), A*02 (P = 0.001, OR 3.02) and HLA-B*07 (P = 0.01, OR 3.27), were significantly associated with autism. Also, the haplotype A*02-B*07 was significantly higher in autistic patients than in controls (P = 0.007, OR 5.83). In class II, DRB1*1104 was significantly higher in patients than in controls (P = 0.001, OR 8.75). The DQB1*0202 (P = 0.001, OR 0.24), DQB1*0302 (P = 0.001, OR 0.14), and DQB1*0501 (P = 0.012, OR 0.25), were negatively associated with disease. While the four-loci genotype study showed that A*01-B*07-DRB1*0701-DQB1*0602 (P = 0.001, OR 41.9) and the A*31-B*51-DRB1*0103-DQB1*0302 (P = 0.012, OR 4.8) are positively associated with autism among Saudi patients. This is the first report on a foreseeable risk of association of HLA-B*07 allele with autism. Thus, HLA-B*07 allele and the closely linked haplotype A*01 B*07 DRB1*0701 DQB1*0602 may serve as a marker for genetic susceptibility to autism in Saudis.
    02/2014; 2014:242048. DOI:10.1155/2014/242048
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    • ". In terms of MHC class III genes, the C4 complement alleles have been linked to ASD [34] [35]. "
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    ABSTRACT: Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental conditions presenting in early childhood with a prevalence ranging from 0.7% to 2.64%. Social interaction and communication skills are impaired and children often present with unusual repetitive behavior. The condition persists for life with major implications for the individual, the family and the entire health care system. While the etiology of ASD remains unknown, various clues suggest a possible association with altered immune responses and ASD. Inflammation in the brain and CNS has been reported by several groups with notable microglia activation and increased cytokine production in postmortem brain specimens of young and old individuals with ASD. Moreover several laboratories have isolated distinctive brain and CNS reactive antibodies from individuals with ASD. Large population based epidemiological studies have established a correlation between ASD and a family history of autoimmune diseases, associations with MHC complex haplotypes, and abnormal levels of various inflammatory cytokines and immunological markers in the blood. In addition, there is evidence that antibodies that are only present in some mothers of children with ASD bind to fetal brain proteins and may be a marker or risk factor for ASD. Studies involving the injection of these ASD specific maternal serum antibodies into pregnant mice during gestation, or gestational exposure of Rhesus monkeys to IgG subclass of these antibodies, have consistently elicited behavioral changes in offspring that have relevance to ASD. We will summarize the various types of studies associating ASD with the immune system, critically evaluate the quality of these studies, and attempt to integrate them in a way that clarifies the areas of immune and autoimmune phenomena in ASD research that will be important indicators for future research.
    Journal of Autoimmunity 07/2013; 44. DOI:10.1016/j.jaut.2013.05.005 · 8.41 Impact Factor
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    • "There is also an increase in the frequency of autoimmune disorders among autistic families (Comi et al., 1999; Sweeten et al., 2003; Atladóttir et al., 2009; Mostafa and Kitchener, 2009; Mostafa and Shehab, 2010; Mostafa et al., 2010a, 2010b). Inspite of the fact that the origins of autoimmunity in autism are unknown, the major histocompatibility complex genes and their products might be involved (Warren et al., 1991; Odell et al., 2005; Mostafa and Shehab, 2010; Mostafa et al., 2013). "
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    ABSTRACT: Etiology of autism has become an area of a significant controversy. Allergy induced autism is an area of research wherein immune responses to some allergens may play a pathogenic role in autism. Allergy may induce the production of brain specific auto-antibodies in a subgroup of autistic children. We are the first to investigate the possible link between allergic manifestations and serum levels of both anti-myelin basic protein (anti-MBP) and anti-myelin associated glycoprotein (anti-MAG) brain-specific auto-antibodies, which were measured by ELISA method, in 42 autistic children in comparison to 42 healthy-matched children. Allergic manifestations (bronchial asthma, atopic dermatitis and/or allergic rhinitis) were found in 47.6% of autistic patients. Increased serum levels of anti-MBP and anti-MAG auto-antibodies were found in 57.1% and 66.7%, respectively of autistic children. In addition, 78.5% of autistic children had increased serum levels of both anti-MBP and/or anti-MAG auto-antibodies. Autistic patients with allergic manifestations had significantly higher serum levels of anti-MBP and anti-MAG auto-antibodies than those without these manifestations (P<0.001 and P=0.001, respectively). In conclusion, allergy may be a contributing factor to the increased serum levels of anti-MBP and anti-MAG auto-antibodies in some autistic children. Indeed, we need to know more about the links between allergy, immune system and brain in autism for finding new therapeutic modalities in autism.
    Journal of neuroimmunology 05/2013; 261(1-2). DOI:10.1016/j.jneuroim.2013.04.003 · 2.47 Impact Factor
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