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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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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
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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
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author 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
author_facet 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
author_sort Ramwadhdoebe, Tamara H
collection PubMed
description 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.
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spelling pubmed-65324482019-05-28 Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis 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 Rheumatology (Oxford) Clinical Science 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. Oxford University Press 2019-06 2019-01-10 /pmc/articles/PMC6532448/ /pubmed/30649469 http://dx.doi.org/10.1093/rheumatology/key428 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Science
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
Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title_full Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title_fullStr Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title_full_unstemmed Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title_short Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
title_sort effect of rituximab treatment on t and b cell subsets in lymph node biopsies of patients with rheumatoid arthritis
topic Clinical Science
url 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
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