Carlos R Camara-Lemarroy1, Claudia Silva2, Luanne M Metz2, Graziela Cerchiaro3, Jamie Greenfield3, Reza Dowlatabadi4, Hans J Vogel4, Chieh-Hsin Lee5, Fabrizio Giuliani5, Maryam Nakhaei-Nejad5, David K B Li6, Anthony Traboulsee6, V Wee Yong2. 1. Departments of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: Carlos.Camara-Lemarroy@albertahealthservices.ca. 2. Departments of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 3. Departments of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 4. Department of Biological Science, Bio-NMR-metabolomics Research center, University of Calgary, Calgary, Canada. 5. Department of Medicine, University of Alberta, Alberta, Canada. 6. Department of Medicine, University of British Columbia, Canada.
Abstract
BACKGROUND: Increasing evidence suggests that various inflammatory, immunological and metabolic pathways are altered in the clinically isolated syndrome (CIS) of multiple sclerosis (MS). Moreover, recent diagnostic criteria have made possible the very early diagnosis of MS. We evaluated multiple fluid biomarkers in people with early MS and CIS. METHODS: We measured blood levels of cytokines, matrix metalloproteinases (MMPs), serum metabolomics and immune cell immunophenotyping in participants in the Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. RESULTS: When compared with healthy controls, people with early MS/CIS had higher levels of eotaxin, MCP-3, IL-1 receptor antagonist, IL-1β, IL-9 and IP-10, as well as MMPs 1, 8 and 9. In metabolomics analysis, the alanine, aspartate and glutamate metabolism and the synthesis and degradation of ketone bodies pathways were altered compared to healthy controls. There were no differences in lymphocyte subpopulation numbers. Out of all these biomarkers, only MMP-1 was able to differentiate between early MS and CIS, and was found to correlate with lesion volume and gadolinium enhancing lesions on MRI. CONCLUSION: The immunological and metabolic profile of CIS and early MS is remarkably similar, supporting that these are a continuum of a common underlying pathophysiological process.
BACKGROUND: Increasing evidence suggests that various inflammatory, immunological and metabolic pathways are altered in the clinically isolated syndrome (CIS) of multiple sclerosis (MS). Moreover, recent diagnostic criteria have made possible the very early diagnosis of MS. We evaluated multiple fluid biomarkers in people with early MS and CIS. METHODS: We measured blood levels of cytokines, matrix metalloproteinases (MMPs), serum metabolomics and immune cell immunophenotyping in participants in the Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. RESULTS: When compared with healthy controls, people with early MS/CIS had higher levels of eotaxin, MCP-3, IL-1 receptor antagonist, IL-1β, IL-9 and IP-10, as well as MMPs 1, 8 and 9. In metabolomics analysis, the alanine, aspartate and glutamate metabolism and the synthesis and degradation of ketone bodies pathways were altered compared to healthy controls. There were no differences in lymphocyte subpopulation numbers. Out of all these biomarkers, only MMP-1 was able to differentiate between early MS and CIS, and was found to correlate with lesion volume and gadolinium enhancing lesions on MRI. CONCLUSION: The immunological and metabolic profile of CIS and early MS is remarkably similar, supporting that these are a continuum of a common underlying pathophysiological process.
Authors: Carlos Camara-Lemarroy; Luanne Metz; Jens Kuhle; David Leppert; Eline Willemse; David Kb Li; Anthony Traboulsee; Jamie Greenfield; Graziela Cerchiaro; Claudia Silva; V Wee Yong Journal: Mult Scler Date: 2022-07-18 Impact factor: 5.855