Recent advances in the immunology of multiple sclerosis.

Introduction. Multiple sclerosis (MS) is a heterogeneous disease. From an immunological point of view, it is considered an inflammatory TH1-mediated autoimmune disease of unknown origin, targeting myelin proteins. State of art. Neuropathological analysis of MS lesions classified different clinical MS types according to the preponderance of different subsets of immune cells in the lesions (clinico-pathological correlation). Ex vivo analysis of various immunological parameters (like cytokines, antigenic targets) and MRI findings suggest a heterogeneous process leading to the autoimmune destruction of the myelin sheath. Clinical therapeutic trials, especially those using monoclonal antibodies, have recently improved our understanding of the immunology of MS, by focusing our interest on molecules modulating the reactivity of T or B cells, and on the influence of adhesion molecules on relapsing remititing MS. Finally, large scale transcriptional analysis of MS and EAE lesions gave a large amount of information about molecules that are up or down regulated during the disease process, and identified new candidates like osteopontin, which ended up being a key proinflammatoty molecule influencing the course of the disease and a therapeutic target for EAE. Perspectives. Investigating the numerous MS and EAE large scale transcriptional profiles will allow new hypotheses to arise, especially in the immunological field of MS. The relationship between inflammation and axonal loss is one of the key questions raised by researchers, and whether these two processes are directly related or not is still debated today. Conclusion. A better understanding of the immunology of MS would lead to the discovery of new therapeutic and biological tools, allowing practical improvement of MS patient care.