High-throughput autoantibody screening identifies differentially abundant autoantibodies in autism spectrum disorder

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Mohamed M. Emara¹  Omar Albagha²  Abdelilah Arredouani³  Lawrence W. Stanton⁴  Fouad Al-Shaban⁴  Omar M. A. El-Agnaf⁴  Areej Mesleh⁴  Hanan Ehtewish⁴  Houari B. Abdesselem⁵  Julie Decock⁶  Nehad M. Alajez⁶  Sara A. Abdulla⁷  Katie Lennard⁸  Jonathan M. Blackburnand⁹ 

[1] Basic Medical Sciences Department, College of Medicine, Qatar University Health, Qatar University, Doha, Qatar;College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar;College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Proteomics Core Facility, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Translational Cancer and Immunity Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar;Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur, Malaysia;Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur, Malaysia;Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;

关键词: autism spectrum disorder;    autoantibodies;    profiling;    pathways;    biomarker;   

DOI  :  10.3389/fnmol.2023.1222506

 received in 2023-05-14, accepted in 2023-09-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by defects in two core domains, social/communication skills and restricted/repetitive behaviors or interests. There is no approved biomarker for ASD diagnosis, and the current diagnostic method is based on clinical manifestation, which tends to vary vastly between the affected individuals due to the heterogeneous nature of ASD. There is emerging evidence that supports the implication of the immune system in ASD, specifically autoimmunity; however, the role of autoantibodies in ASD children is not yet fully understood.Materials and methodsIn this study, we screened serum samples from 93 cases with ASD and 28 healthy controls utilizing high-throughput KoRectly Expressed (KREX) i-Ome protein-array technology. Our goal was to identify autoantibodies with differential expressions in ASD and to gain insights into the biological significance of these autoantibodies in the context of ASD pathogenesis.ResultOur autoantibody expression analysis identified 29 differential autoantibodies in ASD, 4 of which were upregulated and 25 downregulated. Subsequently, gene ontology (GO) and network analysis showed that the proteins of these autoantibodies are expressed in the brain and involved in axonal guidance, chromatin binding, and multiple metabolic pathways. Correlation analysis revealed that these autoantibodies negatively correlate with the age of ASD subjects.ConclusionThis study explored autoantibody reactivity against self-antigens in ASD individuals' serum using a high-throughput assay. The identified autoantibodies were reactive against proteins involved in axonal guidance, synaptic function, amino acid metabolism, fatty acid metabolism, and chromatin binding.

【 授权许可】

Unknown   
Copyright © 2023 Mesleh, Ehtewish, Lennard, Abdesselem, Al-Shaban, Decock, Alajez, Arredouani, Emara, Albagha, Stanton, Abdulla, Blackburnand and El-Agnaf.