Pro-inflammatory adiponectin in pediatric-onset multiple sclerosis-Reference-Cited by-同舟云学术

Pro-inflammatory adiponectin in pediatric-onset multiple sclerosis

Published:2021-02-01 Issue:12 Volume:27 Page:1948-1959
ISSN:1352-4585
Container-title:Multiple Sclerosis Journal
language:en
Short-container-title:Mult Scler

Author:

Nyirenda Mukanthu H¹,Fadda Giulia²^ORCID,Healy Luke M³,Mexhitaj Ina²,Poliquin-Lasnier Laurence⁴,Hanwell Heather⁵,Saveriano Alexander W³,Rozenberg Ayal⁶,Li Rui²,Moore Craig S⁷,Belabani Chahrazed⁸,Johnson Trina⁸,O’Mahony Julia⁹,Arnold Douglas L³,Yeh E Ann¹⁰^ORCID,Marrie Ruth Ann¹¹^ORCID,Dunn Shannon¹²,Banwell Brenda¹³,Bar-Or; Amit¹⁴

Affiliation:

1. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

2. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

3. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

4. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Hull Hospital, Gatineau, QC, Canada

5. Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, ON, Canada/ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

6. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Neuroimmunology Unit, Rambam Health Care Campus, Haifa, Israel

7. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada

8. Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, QC, Canada

9. Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, ON, Canada

10. Division of Neurology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada

11. Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MN, Canada

12. Keenan Research Centre for Biomedical Science, Toronto, ON, Canada/Department of Immunology, University of Toronto, Toronto, ON, Canada

13. Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, ON, Canada/Division of Neurology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada/Division of Child Neurology, Children’s Hospital of Philadelphia, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

14. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Abstract

Background: Being obese is associated with both increased risk of developing multiple sclerosis (MS) and greater MS disease activity. Objectives: The objective of this study is to investigate levels and potential pathophysiologic contribution of serum adipose-hormones (adipokines) in pediatric-onset MS. Methods: Following a Luminex adipokine screen, adiponectin (APN) and its isoforms were quantified by enzyme-linked immunosorbent assay (ELISA) in 169 children with incident acquired demyelinating syndromes (ADS), prospectively ascertained as having either MS or other forms of inflammatory central nervous system (CNS) demyelination. The effect of recombinant APN and APN-containing sera was assessed on functional responses of normal human peripheral blood myeloid and T cells and on human CNS-derived microglia. Results: Compared to other cohorts, children with MS harbored higher serum APN levels, principally driven by higher levels of the low-molecular-weight isoform. Recombinant APN and pediatric MS serum-induced APN-dependent pro-inflammatory activation of CD14+ monocytes and of activated CD4+ and CD8+ T cells (both directly and indirectly through myeloid cells). APN induced human microglia activation while inhibiting their expression of molecules associated with quiescence. Conclusions: Elevated APN levels in children with MS may contribute to enhanced pro-inflammatory states of innate and adaptive peripheral immune responses and breach CNS-resident microglia quiescence, providing a plausible and potentially targetable mechanism by which APN contributes to MS disease activity.

Funder

multiple sclerosis scientific research foundation

university of pennsylvania

multiple sclerosis society of canada

american academy of neurology

canadian institutes of health research

national multiple sclerosis society

national institutes of health

immune tolerance network

Publisher

SAGE Publications

Subject