Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Autoimmunity / genetics Child Female Humans Immunity, Innate / genetics Infant, Newborn Inflammation / genetics Obsessive-Compulsive Disorder / genetics Pregnancy Tic Disorders Tics Transcriptome
Autoimmune disease Cytokines Inflammation Innate immunity Maternal immune activation Neurodevelopmental disorders Obsessive–compulsive disorder Tics Tourette syndrome Transcriptome

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
05 2021
Historique:
received: 03 10 2020
revised: 12 12 2020
accepted: 31 12 2020
pubmed: 11 1 2021
medline: 29 5 2021
entrez: 10 1 2021
Statut: ppublish

Résumé

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.

Identifiants

DOI: 10.1016/j.bbi.2020.12.035 PMID: 33422639
pubmed: 33422639
pii: S0889-1591(21)00004-0
doi: 10.1016/j.bbi.2020.12.035
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

308-317

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH103339
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103365
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103392
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103340
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103346
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105472
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094714
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105898
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH102791
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH105881
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH103877
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH106934
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Hannah F Jones (HF)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Neuroservices, Starship Children's Hospital, Auckland, New Zealand; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Velda X Han (VX)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.

Shrujna Patel (S)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Brian S Gloss (BS)

Westmead Research Hub, Westmead Institute for Medical Research, Westmead, Sydney, New South Wales, Australia.

Nicolette Soler (N)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Psychological Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Alvin Ho (A)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong.

Suvasini Sharma (S)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Neurology Division, Department of Paediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India.

Kavitha Kothur (K)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Margherita Nosadini (M)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Paediatric Neurology Unit, Department of Paediatrics, University of Padua, Italy.

Louise Wienholt (L)

The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

Chris Hardwick (C)

Department of Psychological Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Elizabeth H Barnes (EH)

NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Jacqueline R Lim (JR)

The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Sarah Alshammery (S)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Timothy C Nielsen (TC)

Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Melanie Wong (M)

Department of Immunology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Markus J Hofer (MJ)

School of Life and Environmental Sciences and Charles Perkins Centre, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.

Natasha Nassar (N)

Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Wendy Gold (W)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Medical Research Institute, Westmead, Sydney, New South Wales, Australia.

Fabienne Brilot (F)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.

Shekeeb S Mohammad (SS)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Russell C Dale (RC)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; The Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia. Electronic address: russell.dale@sydney.edu.au.

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Classifications MeSH

questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Auto-immunité › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Troubles mentaux › Troubles anxieux › Trouble obsessionnel compulsif › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles des tics › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Dyskinésies › Tics › Maternal autoimmunity and inflammation are...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Maternal autoimmunity and inflammation are...