Dysregulation of the expression of HLA-DR, costimulatory molecule, and chemokine receptors on immune cells in children with autism.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous disorder diagnosed based on the severity of abnormalities in social skills. Several studies have acknowledged the presence of abnormal immune functions among individuals diagnosed with ASD. HLA-DR (human leukocyte antigen-antigen D related) has been shown to play a significant role in several inflammatory and neurological disorders; however, the role of HLA-DR signaling in ASD has not yet been fully clarified. In this study, we investigated the role of HLA-DR signaling in children with ASD. Flow cytometric analysis, using peripheral blood mononuclear cells (PBMCs), revealed the numbers of CD4+, CD8+, CD28+, CXCR4+, and CCR7+ expressing HLA-DR cells in typically developing (TD) controls and children with ASD. We also determined the numbers of IFN-γ+, IL-21+, and Foxp3+ expressing HLA-DR cells in TD controls and in children with ASD using PBMCs. We observed mRNA and protein expression levels of HLA-DR by RT-PCR and western blotting analysis. Our results revealed that children with ASD had significantly increased numbers of HLA-DR+CD4+, HLA-DR+CD8+, CD28+HLA-DR+, HLA-DR+CXCR4+, HLA-DR+CCR7+ cells compared with TD controls. We found that children with ASD showed increased HLA-DR+IFN-γ+ and HLA-DR+IL-21+ and decreased HLA-DR+Foxp3+ expression levels compared with TD controls. Furthermore, children with ASD showed higher HLA-DR mRNA and protein expression levels compared with TD controls. These results indicated that HLA-DR could play an essential role in the immune abnormalities associated with ASD.

• Authors: Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Laila Y Al-Ayadhi, Moureq R Alotaibi, Ali R Alhoshani, Khaled A Al-Hosaini, Sabry M Attia
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 65 Pg. 360-365 (Dec 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30380510 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, CD
• Costimulatory and Inhibitory T-Cell Receptors
• FOXP3 protein, human
• Forkhead Transcription Factors
• HLA-DR Antigens
• Interleukins
• Receptors, Chemokine
• Interferon-gamma
• interleukin-21

Topics

• Antigens, CD (metabolism)
• Autism Spectrum Disorder (immunology)
• Cell Separation
• Cells, Cultured
• Child
• Child, Preschool
• Costimulatory and Inhibitory T-Cell Receptors (metabolism)
• Flow Cytometry
• Forkhead Transcription Factors (metabolism)
• HLA-DR Antigens (metabolism)
• Humans
• Immunophenotyping
• Interferon-gamma (metabolism)
• Interleukins (metabolism)
• Lymphocyte Activation
• Receptors, Chemokine (metabolism)
• Signal Transduction
• T-Lymphocytes (immunology)