The autoimmune concept of multiple sclerosis

Abstract : Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). With growing evidence for environmental and genetic factors, MS is now accepted as an autoimmune disease. This complex disease seems to implicate various cell types in both innate and adaptive compartments. Here, we discuss recent advances in the immunological field of MS research. Medical literature commonly refers to multiple sclerosis (MS) as the most common autoim-mune disease of the central nervous system. Certainly, the disease is common, at least in the temperate climate zones of the Northern hemisphere. But is it an autoimmune disease? It is safe to say that indeed there are several lines of evidence indicating that MS is the result of an autoimmune attack against the brain white matter. It should be noted however that all these arguments are indirect, but afford no formal proof. Evidence in support of an autoimmune pathogenesis includes the morphology of inflammatory lesions (perivascular infiltrates with parenchymal invasion, activation of potential APCs), the clonal expansion of infiltrating T cells (with silent mutations), the presence of oligoclonal Ig bands in CSF formed mostly by local B lymphocytes (of unknown specificity), the presence of circulating autoantibodies directed against autoantigens like the glial potassium channel autoantigen Kir4.1, which are seen in some, not all patients, and anti-MOG in subsets of (infantile) MS. Furthermore, genetic risk factors-as identified by recent Genome wide association studies (GWAS)-mostly implicate immune genes. Then animal autoimmune models with MS-like morphology provide additional support to the active role of the immune system. Finally, therapies targeting inflammatory and immune processes show a strong protective effect against the formation of new lesions. In the following paragraphs, we will summarize recent research detailing these individual issues.
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Bryan Nicol, Marion Salou, David-Axel Laplaud, Hartmut Wekerle. The autoimmune concept of multiple sclerosis. La Presse Médicale, Elsevier Masson, 2015, 44 (4), pp.e103-e112. ⟨10.1016/j.lpm.2015.02.009⟩. ⟨inserm-02147770⟩

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