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A contribution from complement has long been suspected, based on the results of pathological and functional studies which have demonstrated complement activation products in MS brain and biological fluids. However, the extent and nature of complement activation and its contribution to disease phenotype and long-term outcome remain unclear. Furthermore, functional polymorphisms in components and regulators of the complement system which cause dysregulation, and are known to contribute to other autoimmune inflammatory disorders, have not been investigated to date in MS in any detail. In this paper we review evidence from pathological, animal model and human functional and genetic studies, implicating activation of complement in MS. We also evaluate the potential of complement components and regulators and their polymorphic variants as biomarkers of disease, and suggest appropriate directions for future research.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2008.03830.x","type":"journal-article","created":{"date-parts":[[2008,11,27]],"date-time":"2008-11-27T13:57:39Z","timestamp":1227794259000},"page":"128-139","source":"Crossref","is-referenced-by-count":94,"title":["Complement in multiple sclerosis: its role in disease and potential as a biomarker"],"prefix":"10.1093","volume":"155","author":[{"given":"G","family":"Ingram","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Cardiff University, Heath Park"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Hakobyan","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Immunology, Cardiff University, Heath Park, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N P","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cardiff University, Heath Park"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B P","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Immunology, Cardiff University, Heath Park, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,11,27]]},"reference":[{"key":"2022010404534893200_b1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0140-6736(02)08220-X","article-title":"Multiple sclerosis","volume":"359","author":"Compston","year":"2002","journal-title":"Lancet"},{"key":"2022010404534893200_b2","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/ni1507","article-title":"Multiple sclerosis: a complicated picture of autoimmunity","volume":"8","author":"McFarland","year":"2007","journal-title":"Nat Immunol"},{"key":"2022010404534893200_b3","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1136\/jnnp.2007.133785","article-title":"Change in disability in patients with multiple sclerosis: a 20-year prospective population-based analysis","volume":"79","author":"Hirst","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2022010404534893200_b4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.clineuro.2004.02.007","article-title":"The pathogenesis and basis for treatment in multiple sclerosis","volume":"106","author":"Compston","year":"2004","journal-title":"Clin Neurol Neurosurg"},{"issue":"3","key":"2022010404534893200_b5","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1212\/01.wnl.0000275229.13012.32","article-title":"Pathogenesis of axonal and neuronal damage in multiple sclerosis","volume":"68","author":"Dutta","year":"2007","journal-title":"Neurology"},{"key":"2022010404534893200_b6","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0006-8993(71)90052-7","article-title":"The immunogenesis of the multiple sclerosis plaque","volume":"28","author":"Lumsden","year":"1971","journal-title":"Brain Res"},{"key":"2022010404534893200_b7","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1097\/01.jnen.0000175643.57245.08","article-title":"Complement as a biomarker in multiple sclerosis","volume":"64","author":"Barnum","year":"2005","journal-title":"J Neuropathol Exp Neurol"},{"key":"2022010404534893200_b8","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJM200104123441506","article-title":"Complement. 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