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.
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HLA-DR4 appears at increased rates in children with autism and in their mothers.
“Multiple studies have suggested HLA-DR4 as another risk factor, appearing at increased rates in children with autism as well as their mothers (Johnson et al, 2009;Lee et al, 2006).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Lee et al, 2006
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- Authors
- Lee, L.-C., Zachary, A. A., Leffell, M. S., Newschaffer, C. J., Matteson, K. J., Tyler, J. D., & Zimmerman, A. W.
- Affiliations
- Johns Hopkins University (US)
- University of Tennessee Medical Center (US)
- Kennedy Krieger Institute (US)
- Corresponding author
- Lee, Li-Ching
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 35
- Issue
- 5
- Pages
- 303-307
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W2037692108
- Cited by
- 106
- References
- 34
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 1 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 12
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (U10/CCU320408-03)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- HLA-DR4, autism spectrum disorder, HLA alleles, maternal-fetal immune interaction, fetal brain development, epigenetic mechanisms
- MeSH terms
- Adult, Autistic Disorder, Catchment Area, Health, Child, Fathers, Female, Gene Frequency, Histocompatibility Testing, Humans, Male, Mothers, United States, HLA-DR4 Antigen, Case-Control Studies, White People
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