Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis

Duda, Petra W.; Schmied, M.; Cook, Sandra; Krieger, Jeffrey; Hafler, David A.

doi:10.1172/jci8970

Cited by 407 publications

(268 citation statements)

References 38 publications

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“…Our own studies suggest that when chronically administered to patients with MS, GA is capable of inducing immune deviation, which may result in amelioration of inflammatory responses (23). The apparent universal immunogenicity of GA suggests the possibility that GA could serve as the ultimate helper epitope.…”

Section: Discussionmentioning

confidence: 85%

“…Our preliminary findings in an earlier study supported this hypothesis. We found that the GA-mediated proliferation of GA-reactive T cell lines was inhibited by the monoclonal anti-DR Ab LB3.1 but not by the monoclonal anti-DQ Ab IVD12 (23). Both LB3.1 and IVD12 have previously been shown to recognize nonpolymorphic determinants present on DR and DQ molecules, respectively, and to inhibit the proliferation of DR-and DQ-restricted T cell responses.…”

Section: Ga-reactive T Cell Lines Are Hla Dr Restrictedmentioning

confidence: 75%

“…On day 10, the contents of each well were evaluated for GA-specific proliferation in a split well assay. The split well assay was conducted as previously described (23). Briefly, the split well assays were established by incubating equal aliquots of a given T cell line with autologous PBMCs, ␥-irradiated with 3000 rad, either pulsed with 20 g/ml GA or no Ag for 1 h in 96-well round bottom microtiter plates in an 8% CO 2 37°C humidified incubator.…”

Section: Generation Of Ga-specific Human T Cell Linesmentioning

confidence: 99%

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Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate

Duda

Krieger

Schmied

et al. 2000

The Journal of Immunology

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The capacity of glatiramer acetate (GA), a random copolymer of alanine, lysine, glutamic acid, and tyrosine to stimulate primary in vitro human and murine T cell proliferation was examined. PBMCs isolated from healthy humans and relapsing remitting multiple sclerosis patients and spleen cells from inbred strains of mice, expressing different H-2 haplotypes, were used as sources of non-GA-primed lymphocytes. GA functioned as a universal Ag, inducing dose-dependent proliferation of all non-GA-primed human and murine T cell populations tested. Moreover, GA stimulated PBMCs derived ex vivo from human cord blood, strongly suggesting that GA can activate both naive and memory T cells. The human T cell proliferative responses to GA were HLA class II DR-restricted by virtue of the ability of anti-class II Ab to inhibit T cell proliferation, and the demonstration that individual GA specific human T cell clones were HLA class II DR-restricted by either restriction element but not both. Furthermore, GA-reactive T cells secreted Th0 cytokines and expressed a diverse repertoire of TCR. Limiting dilution analysis indicated that the T cell precursor frequency among the healthy human adults tested ranged from 1:5,000 to 1:125,000. Given that all of the T cell populations tested were isolated from non-GA-primed donors, it appears that virtually all humans and murine strains contain significant numbers of T cell populations cross-reactive with GA. These findings may explain the recent clinical finding that daily s.c. administration of GA ameliorates the progression of multiple sclerosis.

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Section: Discussionmentioning

confidence: 85%

Section: Ga-reactive T Cell Lines Are Hla Dr Restrictedmentioning

confidence: 75%

Section: Generation Of Ga-specific Human T Cell Linesmentioning

confidence: 99%

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Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate

Duda

Krieger

Schmied

et al. 2000

The Journal of Immunology

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“…In der antiinflammatorische Zytokine (Duda et al 2000). Ob GA über eine Induktion der PHB- (Nijtmans et al 2000).…”

Section: Diskussionunclassified

Proteomanalyse humaner Glatiramerazetat und Myelin basisches Protein spezifischer T-Zell Linien von MS Patienten und gesunden Kontrollpersonen

Knop¹,

Jarstorff²,

Vargas-Leal³

et al. 2007

Akt Neurol

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“…Por outro lado, a ação terapêutica do acetato de glatirâmer é principalmente devida à expansão de células Th2-específicas com propriedades imunoreguladoras 28 . …”

Section: Classificação Das Formas Evolutivas Da Esclerose Múltiplaunclassified

Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: III. Diretrizes baseadas em evidências e recomendações

Lana-Peixoto¹,

Callegaro²,

Moreira³

et al. 2002

Arq. Neuro-Psiquiatr.

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RESUMO -Em razão dos avanços no conhecimento da esclerose múltipla (EM), dos novos critérios diagnósticos e ensaios terapêuticos publicados, a atualização e expansão das diretrizes para orientação do neurologista brasileiro em relação ao tratamento da EM se tornam necessárias. O Consenso Expandido do BCTRIMS enfatiza a individualização do tratamento a critério do neurologista, e a necessidade de informação do paciente quanto aos potenciais benefícios e riscos das drogas, assim como do Consentimento Informado e compromisso de realização de controles periódicos. Na ausência de evidências científicas favorecendo uma determinada droga o médico deve considerar o custo diferencial dos imunomoduladores ao fazer sua opção terapêutica. As várias situações clínicas e os diferentes agentes modificadores da doença, assim como as outras intervenções terapêuticas de eficácia no tratamento são consideradas à luz das classes de evidências científicas e dos tipos de recomendação, aceitos pela comunidade científica internacional. O Consenso Expandido do BCTRIMS pode servir de modelo para outros países em desenvolvimento. PALAVRAS-CHAVE: esclerose múltipla, tratamento, recomendações, imunointervenção. The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: III. Evidence and recommendationbased guidelinesABSTRACT -There has been unprecedented advances in knowledge of multiple sclerosis (MS) in the last few years. A new set of criteria for its diagnosis and a bunch of recent clinical trials with disease-modifying agents (DMA) have been published. All of that has made it necessary to update and expand the previous consensus for MS treatment as formulated by the Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) two years ago. The BCTRIMS Expanded Consensus emphasizes the need to (1) consider MS treatment on an individual basis; (2)

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Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis

Cited by 407 publications

References 38 publications

Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate

Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate

Proteomanalyse humaner Glatiramerazetat und Myelin basisches Protein spezifischer T-Zell Linien von MS Patienten und gesunden Kontrollpersonen

Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: III. Diretrizes baseadas em evidências e recomendações

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