Literature DB >> 19189075

[Targeting B cells in multiple sclerosis. Current concepts and strategies].

T Menge1, H-C Büdingen, M C Dalakas, B C Kieseier, H-P Hartung.   

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the CNS and a leading cause of lasting neurological disability in younger adults. In the last decade our knowledge of its immunopathogenesis expanded vastly. It is now widely appreciated that B cells are key players in the autoreactive immune network. They exert far more functions than merely being the precursors of antibody-producing plasma cells. B cells act as efficient antigen-presenting cells and may stimulate an autoreactive immune response through secretion of proinflammatory cytokines. It is thus only logical to test therapeutic strategies targeting B cells in MS. Rituximab is a depleting chimeric monoclonal antibody directed against CD20 and expressed on developing, naïve, and memory B cells but not stem or plasma cells. Several smaller studies have been conducted that led to a placebo controlled, double blind phase II study on efficacy which was reported recently. The results are very promising, meeting not only the primary endpoint of reduction of the surrogate MRI marker of contrast-enhancing lesions but also showing a reduction in clinical relapse rate of patients treated with rituximab. This review discusses the role of autoreactive B cells in the context of MS, analyzes the B-cell-depleting treatment studies reported, and provides information on planned and future B-cell-directed therapeutic strategies in MS.

Entities:  

Mesh:

Substances:

Year:  2009        PMID: 19189075     DOI: 10.1007/s00115-008-2664-2

Source DB:  PubMed          Journal:  Nervenarzt        ISSN: 0028-2804            Impact factor:   1.214


  77 in total

Review 1.  B-cells in multiple sclerosis.

Authors:  M Duddy; A Bar-Or
Journal:  Int MS J       Date:  2006-11

Review 2.  A decade of rituximab: improving survival outcomes in non-Hodgkin's lymphoma.

Authors:  Arturo Molina
Journal:  Annu Rev Med       Date:  2008       Impact factor: 13.739

3.  Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination.

Authors:  C Lucchinetti; W Brück; J Parisi; B Scheithauer; M Rodriguez; H Lassmann
Journal:  Ann Neurol       Date:  2000-06       Impact factor: 10.422

Review 4.  The role of BAFF in immune function and implications for autoimmunity.

Authors:  Susan L Kalled
Journal:  Immunol Rev       Date:  2005-04       Impact factor: 12.988

5.  Unveiling the enigma of the CNS as a B-cell fostering environment.

Authors:  Antonio Uccelli; Francesca Aloisi; Vito Pistoia
Journal:  Trends Immunol       Date:  2005-05       Impact factor: 16.687

6.  Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis.

Authors:  S Cepok; M Jacobsen; S Schock; B Omer; S Jaekel; I Böddeker; W H Oertel; N Sommer; B Hemmer
Journal:  Brain       Date:  2001-11       Impact factor: 13.501

7.  Fcgamma receptor-dependent effector mechanisms regulate CD19 and CD20 antibody immunotherapies for B lymphocyte malignancies and autoimmunity.

Authors:  Thomas F Tedder; Aris Baras; Yan Xiu
Journal:  Springer Semin Immunopathol       Date:  2006-11-08

8.  Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis.

Authors:  Y Qin; P Duquette; Y Zhang; P Talbot; R Poole; J Antel
Journal:  J Clin Invest       Date:  1998-09-01       Impact factor: 14.808

Review 9.  Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells.

Authors:  Stamatis-Nick C Liossis; Petros P Sfikakis
Journal:  Clin Immunol       Date:  2008-03-11       Impact factor: 3.969

10.  Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5.

Authors:  Christopher D C Allen; K Mark Ansel; Caroline Low; Robin Lesley; Hirokazu Tamamura; Nobutaka Fujii; Jason G Cyster
Journal:  Nat Immunol       Date:  2004-08-01       Impact factor: 25.606

View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.