Future Approaches on Multiple Sclerosis Towards the Immunological and Neuropathological Advances

Yıl 2008, Cilt: 2 Sayı: 1, 274 - 279, 23.03.2008

Bilge Koçer

Öz

Multiple Sclerosis is an inflammatory disease of central nervous system white matter. Although the etiology of multiple sclerosis is still unknown, many findings point a central role for the immune system in the pathogenesis of disease. This is supported by the beneficial effect of immunomodulatory and immunosuppressive therapy on disease activity. Activated myelin reactive T cells as major mediators of the disease. In addition possible contribution of B cells to multiple sclerosis immunopathology has been outlined. The demonstration of distinct pathologic patterns in multiple sclerosis plaques suggests that several mechanisms may contribute to tissue injury and that the prevailing mechanism may not be the same across patients. Existing disease modifying treatments for multiple sclerosis clearly have beneficial effects. However some patients benefiting more than others. Studies on the pathology of multiple sclerosis have demonstrated that there is heterogeneity between different multiple sclerosis patients. Differences in plaque’s pathology may explain the observed heterogeneity of clinical disease course and severity and the different response to therapy. Pathology specific treatment options in multiple sclerosis patients may be more beneficial, but identification of plaques subtype in living patiens is still difficult. In the future with identification of specific pathological subtypes in living patients which will require the identification of specific markers, subsequent specific therapies would be applicable in the patients with the specific pathological characteristics.

Anahtar Kelimeler

Multiple sclerosis, immunology; pathology, , pathology

Multipl Sklerozda İmmünolojik ve Nöropatolojik Gelişmeler Işığında Geleceğe Yönelik Yaklaşımlar

Öz

Multipl Skleroz, santral sinir sistemi beyaz cevherinin inflamatuar hastalığıdır. Multipl Sklerozun etiyolojisinin halen tam olarak bilinmemesine karşılık bazı bulgular hastalığın patogenezinde immün sistemin ana rolüne işaret eder. Bu düşünce immunomodulatuar ve immuno-supresor tedavilerin hastalık aktivitesi üzerindeki faydalı etkileri ile desteklenir. Aktive myelin reaktif T hücreleri hastalıkta majör aracılardır. Ek olarak Multipl Skleroz immunopatolojisinde B hücrelerin muhtemel katkısının altı çizilmektedir. Multipl Skleroz plaklarında farklı patolojik paternlerin gösterilmesi, çeşitli mekanizmaların doku hasarına katkıda bulunabileceğine ve önde giden mekanizmanın hastalarda aynı olmayabileceğine işaret eder. Multipl Sklerozda mevcut olan hastalık modifiye edici tedavilerin açıkça faydalı etkileri vardır. Bununla beraber bu tedavilerden bazı hastalar diğerlerinden daha fazla fayda görmektedir. Multipl Skleroz patolojisi üzerine yapılan çalışmalarda farklı hastalarda heterojenite olduğu gösterildi. Plak patolojisindeki farklılıklar, gözlenen klinik hastalık gidişi ve ciddiyetindeki heterojeniteyi ve hastalarda tedaviye farklı yanıt alınmasını açıklayabilir. Multipl Sklerozlu hastalarda patolojiye özgü tedavi seçenekleri daha faydalı olabilir ancak yaşayan hastalarda plak alt grubunu belirlemek halen çok zor olmaktadır. Gelecekte, hastalarda patolojik alt tiplerin belirlenmesi ile spesifik patolojik özelliği olan hastalara spesifik tedaviler uygulanabilecektir.

Anahtar Kelimeler

Multipl skleroz; immünoloji;, patoloji, , multi

Kaynakça

• 1. Kevin CO, Amit BO, David AH. The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis. J Clinical Immunol 2001;21:81-92.
• 2. Noseworthy JH, Luchinetti C, Rodriguez M, Weinschenker BG. Multiple Sclerosis. N Engl J Med 2000;343:938-52.
• 3. Hemmer B, Nessler S, Zhou D, Kieseier B, Hartung HP. Immunopathogenesis and Immu-notheraphy of Multiple Sclerosis. Nature Clinical Practice Neurology 2006;2:201 -11.
• 4. Gran B, Hemmer B, Vergelli M, McFarland HF, Martin R. Molecular mimic and multiple sclerosis: Degenerate T cell recognition and the induction of autoimmunity. Ann Neurol 1999;45:559-67.
• 5. Springer TA. Traffic signals for lymphocyte recirculation and leucocyte emigration: The multistep paradigm. Cell 1994;76:301-14.
• 6. Raine CS. The Immunology of multiple sclerosis lesion. Ann Neurol 1994;S61-S72.
• 7. Butcher EC. Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell 1991;67:1033-6.
• 8. Ransohoff RM. Mechanisms of inflammation in MS tissue: Adhesion molecules and chemokines. J Neuroimmunol 1999;98:57-68.
• 9. Sobel RA, Mitchel ME, Fondren G. Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in human central nervous system. Am J Pathol 1990;136: 1309-16.
• 10. Cannela B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995;37:424-35.
• 11. Bo L, Peterson JW, Mork S, Hofman PA, Gallatin WM, Ransohof RM, et al. Distribution of immunglobulin superfamily members ICAM-1 ,-2,-3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions. J. Neuropathol Exp Neurol 1996;55:1060-72.
• 12. Zhang GX, Baker CM, Kolson DL, Rostami AM. Chemokines and chemokine receptors in pathogenesis of multiple sclerosis. Mult Scler 2000;6:3-13.
• 13. Leppert D, Waubant E, Galardy R, Bunnet NW, Hauser SL. T cell gelatinases mediated basement membrane transmigration in vitro. J Immunol 1995;154:4379-89.
• 14. Maeda A, Sobel RA. Matrix metalloproteinases in normal human central nervous system, microglial nodules and multiple sclerosis lesions. J Neuropathol Exp Neurol 1996;55:300-9.
• 15. Anthony DC, Miller KM, Fearn S, Townsend MJ, et al. Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS. J Neuroimmunol 1998;87:62-72.
• 16. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 1990;346: 183-7.
• 17. Zhang J, Markovic-Plese S, Lancet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific form myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 1994;179:973-84.
• 18. Cross AH et al. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol 2001;112:1-14.
• 19. Dean M Wingerchuck and Claudşa F. Lucchi-netti: Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis. Curr Opin Neurol 2007;20:343-50.
• 20. Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 2005;201:195-200.
• 21. Genain CP, Cannela B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999;5:170-5.
• 22. Cepok S, et al. The immune response at onset and during recovery from Borrelia burgdorferi meningoradiculitis. Arc Neurol 2003;60: 849-55.
• 23. Frohman EM, Racke MK, Raine CS. Multiple Sclerosis: the plaque and its pathogenesis. N Eng J Med 2006;354:942-55.
• 24. Lucchinetti C, Bruck W, Parisi J, et al. Hete-rogenity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-17.
• 25. Ludwin SK. The pathogenesis of multiple sclerosis: relating human pathology to experimental studies. J Neuropathol Exp Neurol 2006;65:305-18.
• 26. Tarpp BD, Peterson J, Ransohof RM, Rudick R, Mörk M, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278-85.
• 27. Kuhlman T, Lingfeld G, Bitsch A, Schuchardt J, Brück W. Acute axonal damage in multiple sclerosis in most extensive in early disease stages and decreases over time. Brain 2002;125:2202-12.
• 28. Brück W. Clinical implications of neuropatho-logical findings in multiple sclerosis. J Neurol 2005;252(suppl 3)111/10-1114.
• 29. Lucchinetti C, Brück W, Noseworthy J. Multiple Sclerosis: recent developments in neuropathology, pathogenesis, magnetic resonance imaging studies and treatment. Curr Opin Neurol 2001;14:259-69.
• 30. Lucchinetti CF, Mandler RN, MacGavem D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002;125:1450-61.
• 31. Brück W, Lucchinetti C, Lassmann H. The pathology of primary progressive multiple sclerosis. Mult Scler 2002;8:93-7.
• 32. Trap BD, Ransohoff R, Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 1999;12:295-302.
• 33. Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and theraphy. Trends Mol Med 2001;7:115-21.
• 34. Lassman H, Reindl M, Rauschka H et al. A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions. Brain 2003;126 (Pt 6): 1347-57.