Glatiramer Acetate Treatment of Multiple Sclerosis: An Immunological Perspective

Racke, Michael K.; Lovett-Racke, Amy E.

doi:10.4049/jimmunol.1090138

Cited by 46 publications

(30 citation statements)

References 41 publications

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“…This is what we observe in autoimmune diseases like MS where anti-MBP lymphocytes and antibodies participate in CNS damage, under these conditions, the uncontrolled autoreactive reaction causes tissue destruction and aggravates the neurological impairment of patients. On the other hand, the modulation of autoreactive responses has shown to improve morphological and functional outcomes in MS and acute neurodegenerative diseases such as traumatic brain injury (TBI) or SCI [13][14][15]. Accordingly, if the reaction is immediately modulated (by immunizing with neural-derived antigens), even in individuals with the aforementioned factors, the autoreactive response is capable of providing beneficial effects.…”

Section: Discussionmentioning

confidence: 99%

Autoreactivity against myelin basic protein in patients with chronic paraplegia

et al. 2011

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Introduction Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. Materials and methods Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetricBrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. Results SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P \ 0.001). Humoral response analysis yielded a significant difference (P \ 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. Conclusion This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages ([10 years) of injury.

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Section: Discussionmentioning

confidence: 99%

Autoreactivity against myelin basic protein in patients with chronic paraplegia

et al. 2011

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“…GA is a random polymer of glutamic acid, lysine, alanine, and thyrosine, and the amino acid composition of GA is similar to that of myelin basic protein (MBP). 22) GA is thought to act as an altered peptide ligand and to inhibit activation of MBP-specific T cell clones in vitro. 22,23) Thus, the next step will be to establish in detail the mechanism(s) through which clonal selection of autoreactive T cells is prevented by combination therapy with FTY720 and autoantigen.…”

Section: Discussionmentioning

confidence: 99%

Relapse of Experimental Autoimmune Encephalomyelitis after Discontinuation of FTY720 (Fingolimod) Treatment, but Not after Combination of FTY720 and Pathogenic Autoantigen

Yoshida

Tsuji

Fujita

et al. 2011

Biological & Pharmaceutical Bulletin

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FTY720(Fingolimod) is known to have a significant therapeutic effect on experimental autoimmune encephalomyelitis (EAE). Here, we used an EAE mouse model, which had been established by immunizing C57BL/6J mice with a partial peptide of myelin oligodendrocyte glycoprotein (MOG 35-55 ), to examine the relapse of EAE upon discontinuation of treatment with FTY720 alone or in combination with MOG 35-55 . Relapse was confirmed to occur in all animals (n‫)6؍‬ within one week after discontinuation of FTY720, with increase in the number of lymphocytes infiltrating the spinal cord and demyelination. However, in the case of combination therapy with FTY720 and MOG 35-55 , relapse following discontinuation of treatment was completely suppressed. The autoantigenic peptide might serve to suppress the clonal selection of relapse-associated autoantigen-specific T cells.

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“…4 Glatiramer acetate has been shown to affect cells of both the innate and adaptive immune system. 5 The OLYMPUS trial tested rituximab, an anti-CD20, B-cell-depleting recombinant chimeric monoclonal antibody, in a randomized, double-blind, placebocontrolled study design in patients with PPMS. 6 The primary end point, namely confirmed disease progression defined as an increase in the Expanded Disability Status Scale score sustained for 12 weeks, was not reached.…”

Section: Trial Stratificationmentioning

confidence: 99%