title: HLA-DR4 in families with autism.
abstract: Autoimmune disorders are observed with increased frequency among parents of individuals with autism, particularly mothers. Because there is evidence supporting an association between autoimmune disorders and specific alleles of the human leukocyte antigen (HLA) system, we examined HLA types and subtypes in families with autism. Two groups were studied: 16 families selected from a geographically defined area in eastern Tennessee have males with a diagnosis of autism; and 33 families selected across all regions in the United States have multiple males having autism diagnosis. The HLA-DR4 frequencies of mothers, fathers, and children in these two groups were compared with a reference series of 475 normal, unrelated Caucasians. Results of HLA typing indicated that mothers and their sons in the geographically defined group had a significantly higher frequency of DR4 than normal control subjects (odds ratio = 5.54, 95% confidence interval = 1.74-18.67 and odds ratio = 4.20, 95% confidence interval = 1.37-13.27, respectively). No significant difference in the distribution of HLA alleles was evident between the United States-all region group and control subjects. Findings of this study are consistent with a hypothesis that prenatal maternal-fetal immune interaction can affect fetal brain development in a population residing in a geographically defined region. Such immune interactions may involve HLA and related genes in both genetic and epigenetic mechanisms during pregnancy.
authors.affiliation: Center for Autism and Developmental Disabilities Epidemiology, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. llee2@jhsph.edu
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lee
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Newschaffer
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Matteson
authors.forename: John D
authors.initials: JD
authors.lastname: Tyler
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Zimmerman
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002391:Catchment Area, Health; D002648:Child; D005220:Fathers; D005260:Female; D005787:Gene Frequency; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009035:Mothers; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D015804:HLA-DR4 Antigen