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.