A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis
- 738 Downloads
Multiple sclerosis is postulated to be a T cell-mediated autoimmune disease characterised by a relapsing-remitting stage followed by a secondary progressive phase. The relapsing remitting phase may involve waves of proinflammatory Th1 and Th17 cells that infiltrate the nervous system, provoking a clinical attack. The activity of these cells is modulated by other populations of regulatory T cells and the balance between the pro-inflammatory and regulatory T cells is critical for determining disease activity. Promoting the activity of regulatory cells is a potentially beneficial therapeutic strategy, and probably contributes to the action of glatiramer acetate. The progressive phase of multiple sclerosis is believed to be secondary to neurodegenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of multiple sclerosis has been poorly defined until recently. However, recent data suggest that these results demonstrate abnormalities of dendritic cell activation or maturation may underlie the transition to the progressive phase of the disease. Preventing this transition, perhaps by acting at the level of the innate immune system, is an important treatment goal. The identification of biomarkers to predict disease course and treatment response is a major challenge in multiple sclerosis research. Studies using antigen arrays have identified antibody patterns related to CNS antigens and heat-shock proteins that are associated with different disease stages and with response to therapy. In the future, such antibody repertoires could be used as biomarkers for the diagnosis and evaluation of patients with multiple sclerosis, for matching treatments to individual patients and, potentially, to identify healthy individuals at risk for this autoimmune disease.
Key wordsMultiple sclerosis immune system inflammation T-cell regulatory cells innate immune system neurodegeneration
Unable to display preview. Download preview PDF.
- 1.Bakshi R, Neema M, Liptak S, Betensky R, Buckle G, Gauthier S, Stankiewicz J, Meier D, Egorova S, Arora A, Dandamudi V, Batt C, Guss Z, Glanz B, Khoury S, Guttmann C, Weiner H (2007) Magnetic Resonance Disease Severity Scale (MRDSS) Predicts Clinical Progression in Multiple Sclerosis. Neurology 68(Suppl 1):A53CrossRefGoogle Scholar
- 2.Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL (1997) Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proceedings of the National Academy of Sciences of the United States of America 94:599–603PubMedCrossRefGoogle Scholar
- 3.Basso A, Frenkel D, Petrovic-Stojkovic S, Puckett L, Monsonego A, Gozin M, Weiner H (2007) Fullerene (ABS-75) Treatment Reduces Disease Progression and Axonal Loss in MOG-Induced Progressive EAE in NOD Mice. Neurology 68(Suppl 1):A317Google Scholar
- 7.Gauthier S, Liptak S, Polgar-Turcsanyi M, Berger A, Glanz B, Buckle G, Khoury S, Weiner H, Bakshi R, Guttmann C (2007) Benign MS characterized by a lower rate of brain atrophy as compared to early MS. Neurology 68(Suppl 1):A330–A331Google Scholar
- 9.Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL (2007) Risk alleles for multiple sclerosis identified by a genomewide study. The New England Journal of Medicine 357:851–862PubMedCrossRefGoogle Scholar
- 10.Harbo HF, Spurkland A (2007) Genetics in multiple sclerosis: past and future perspectives. Acta Neurol Scand (Suppl 187:)34–38Google Scholar
- 16.Neuhaus O, Farina C, Yassouridis A, Wiendl H, Then Bergh F, Dose T, Wekerle H, Hohlfeld R (2000) Multiple sclerosis: comparison of copolymer-1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. Proceedings of the National Academy of Sciences of the United States of America 97:7452–7457PubMedCrossRefGoogle Scholar
- 19.Quintana F, Viglietta V, Cohen I, Khoury S, Weiner H (2007) Antigen microarrays identify serum biomarkers for multiple sclerosis. Neurology 68(Suppl 1):A399Google Scholar