HLA-DR4 gene expression in a sample of Egyptian autistic children and their mothers: is it a risk factor?

Abstract

Background: Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder without a known cause. However, some autistic children experience immune malfunction and numerous studies noted that probands with autism and their mothers had higher HLA-DR4 frequencies than their fathers did. Probably, the mother's HLA-DR4 activity contributes to the phenotype of autism in her fetus. The purpose of this work was to investigate any potential link between the HLA-DR4 gene and autism. Methods: We conducted a controlled cross-sectional study on 100 subjects enrolled from the Children's Hospital of Ain Shams University. They comprised four groups: 25 autistic children, 25 mothers of the autistic children, 25 healthy children as a control group, and 25 mothers of the healthy children. All children underwent a detailed history taking, general and neurological examination, and IQ assessment using the Stanford Binet scale. Molecular HLA-DR typing was assessed in all subjects. The diagnosis of ASD was established using the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Severity was assessed using the childhood autism rating scale (CARS). Results: 45.5% of the autistic patients demonstrated the HLA DR4 allele compared to 36% of the control children. Up to 9.1% of cases of ASD had a double DR4 allele compared to 4% of the controls but with no significant statistical difference in-between. Also, 48 % of the autistic children's' mothers had the HLA DR4 allele compared to 24% of the control mothers but the difference did not reach a significant difference. On the other hand, the HLA DR3 haplotype was present in only 6.8 % of the patients' alleles compared to 24% of controls (p<0.05). Conclusion: The link of some HLA alleles to autism indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Wider scale studies are needed to validate our findings.