Immunogenetics of autism spectrum disorder: A systematic literature review

Martina Arenella; Rugile Matuleviciute; Ryad Tamouza; Marion Leboyer; Grainne McAlonan; Janita Bralten; Declan Murphy

doi:10.1016/j.bbi.2023.09.010

Immunogenetics of autism spectrum disorder: A systematic literature review

Brain Behav Immun. 2023 Nov:114:488-499. doi: 10.1016/j.bbi.2023.09.010. Epub 2023 Sep 16.

Authors

Martina Arenella¹, Rugile Matuleviciute², Ryad Tamouza³, Marion Leboyer³, Grainne McAlonan⁴, Janita Bralten⁵, Declan Murphy⁴

Affiliations

¹ Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute of Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. Electronic address: martina.arenella@kcl.ac.uk.
² Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; MRC Centre for Neurodevelopmental Disorders, King's College London, London, United Kingdom.
³ University Paris Est Créteil (UPEC), INSERM, IMRB, Translational Neuropsychiatry Lab, AP-HP, Department of Addiction and Psychiatry (DMU IMPACT, FHU ADAPT), France; Fondation FondaMental, F-94010 Créteil, France.
⁴ Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.
⁵ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute of Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.

PMID: 37717669
DOI: 10.1016/j.bbi.2023.09.010

Abstract

The aetiology of autism spectrum disorder (ASD) is complex and, partly, accounted by genetic factors. Nonetheless, the genetic underpinnings of ASD are poorly defined. The presence of immune dysregulations in autistic individuals, and their families, supports a role of the immune system and its genetic regulators. Albeit immune responses belong either to the innate or adaptive arms, the overall immune system genetics is broad, and encompasses a multitude of functionally heterogenous pathways which may have different influences on ASD. Hence, to gain insights on the immunogenetic underpinnings of ASD, we conducted a systematic literature review of previous immune genetic and transcription studies in ASD. We defined a list of immune genes relevant to ASD and explored their neuro-immune function. Our review confirms the presence of immunogenetic variability in ASD, accounted by inherited variations of innate and adaptive immune system genes and genetic expression changes in the blood and post-mortem brain of autistic individuals. Besides their immune function, the identified genes control neurodevelopment processes (neuronal and synaptic plasticity) and are highly expressed in pre/peri-natal periods. Hence, our synthesis bolsters the hypothesis that perturbation in immune genes may contribute to ASD by derailing the typical trajectory of neurodevelopment. Our review also helped identifying some of the limitations of prior immunogenetic research in ASD. Thus, alongside clarifying the neurodevelopment role of immune genes, we outline key considerations for future work into the aetiology of ASD and possible novel intervention targets.

Publication types

Review