Pro-inflammatory adiponectin in pediatric-onset multiple sclerosis.
Autor: | Nyirenda MH; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK., Fadda G; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Healy LM; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada., Mexhitaj I; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Poliquin-Lasnier L; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Hull Hospital, Gatineau, QC, Canada., Hanwell H; 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., Saveriano AW; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada., Rozenberg A; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Neuroimmunology Unit, Rambam Health Care Campus, Haifa, Israel., Li R; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Moore CS; 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., Belabani C; Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, QC, Canada., Johnson T; Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, QC, Canada., O'Mahony J; Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, ON, Canada., Arnold DL; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada., Yeh EA; Division of Neurology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada., Marrie RA; Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MN, Canada., Dunn S; Keenan Research Centre for Biomedical Science, Toronto, ON, Canada/Department of Immunology, University of Toronto, Toronto, ON, Canada., Banwell B; 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., Bar-Or A; 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. |
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Jazyk: | angličtina |
Zdroj: | Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2021 Oct; Vol. 27 (12), pp. 1948-1959. Date of Electronic Publication: 2021 Feb 01. |
DOI: | 10.1177/1352458521989090 |
Abstrakt: | 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. |
Databáze: | MEDLINE |
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