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Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis

OBJECTIVES: The exact underlying mechanism of rituximab treatment in patients with RA is poorly defined and knowledge about the effect of B cell depletion on immune cells in secondary lymphoid organs is lacking. We analysed lymphoid tissue responses to rituximab in RA patients. METHODS: Fourteen RA...

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Detalles Bibliográficos
Autores principales: Ramwadhdoebe, Tamara H, van Baarsen, Lisa G M, Boumans, Maria J H, Bruijnen, Stefan T G, Safy, Mary, Berger, Ferco H, Semmelink, Johanna F, van der Laken, Conny J, Gerlag, Danielle M, Thurlings, Rogier M, Tak, Paul P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532448/
https://www.ncbi.nlm.nih.gov/pubmed/30649469
http://dx.doi.org/10.1093/rheumatology/key428
Descripción
Sumario:OBJECTIVES: The exact underlying mechanism of rituximab treatment in patients with RA is poorly defined and knowledge about the effect of B cell depletion on immune cells in secondary lymphoid organs is lacking. We analysed lymphoid tissue responses to rituximab in RA patients. METHODS: Fourteen RA patients received 2 × 1000 mg rituximab intravenously, and lymph node (LN) biopsies were obtained before and 4 weeks after the first infusion. Tissues were examined by flow cytometry, immunohistochemistry and quantitative PCR. LN biopsies from five healthy individuals (HC) served as controls. RESULTS: LN biopsies of RA patients showed increased frequencies of CD21(+)CD23(+)IgD(high)IgM(variable) follicular B cells and CD3(+)CD25(+)CD69(+) early activated, tissue resident T cells when compared with HCs. After treatment, there was incomplete depletion of LN B cells. There was a significant decrease in CD27(−)IgD(+) naïve B cells, and CD27(+)IgD(+) unswitched memory B cells including the CD27(+)IgD(+)IgM(+) subset and follicular B cells. Strikingly, CD27(+)IgD(−) switched memory B cells persisted in LN biopsies after rituximab treatment. In the T cell compartment, a significant decrease was observed in the frequency of early activated, tissue resident T cells after rituximab treatment, but late activated T cells persisted. B cell proliferation inducing cytokine IL-21 was higher expressed in LN biopsies of RA patients compared with HC and expression was not affected by rituximab treatment. CONCLUSION: Rituximab does not cure RA, possibly due to persistence of switched memory B cells in lymphoid tissues suggesting that factors promoting B cell survival and differentiation need to be additionally targeted.