Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells
(2024) In Arthritis Research and Therapy 26(1).- Abstract
Background: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Methods: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited.... (More)
Background: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Methods: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. Results: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Conclusions: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.
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- author
- Thorarinsdottir, Katrin ; McGrath, Sarah ; Forslind, Kristina LU ; Agelii, Monica Leu ; Ekwall, Anna Karin Hultgård ; Jacobsson, Lennart T.H. ; Rudin, Anna ; Mårtensson, Inga Lill and Gjertsson, Inger
- organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cartilage destruction, CD21 DN B cells, Early rheumatoid arthritis
- in
- Arthritis Research and Therapy
- volume
- 26
- issue
- 1
- article number
- 23
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:38225658
- scopus:85182496927
- ISSN
- 1478-6354
- DOI
- 10.1186/s13075-024-03264-2
- language
- English
- LU publication?
- yes
- id
- f51cf6d1-30c8-4d85-8bc1-03a1b75b99a6
- date added to LUP
- 2024-02-20 14:56:32
- date last changed
- 2024-04-20 14:11:18
@article{f51cf6d1-30c8-4d85-8bc1-03a1b75b99a6,
abstract = {{<p>Background: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21<sup>−/low</sup> B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21<sup>+</sup> and CD21<sup>−/low</sup> B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Methods: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. Results: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21<sup>+</sup> B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21<sup>+</sup>CD27<sup>+</sup> subsets and CD21<sup>−/low</sup> CD27<sup>+</sup>IgD<sup>+</sup> subset. The only B cell subset found to associate with clinical factors was the CD21<sup>−/low</sup> double-negative (DN, CD27<sup>−</sup>IgD<sup>−</sup>) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21<sup>−/low</sup> DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Conclusions: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21<sup>−/low</sup> DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21<sup>−/low</sup> DN in RA pathogenesis.</p>}},
author = {{Thorarinsdottir, Katrin and McGrath, Sarah and Forslind, Kristina and Agelii, Monica Leu and Ekwall, Anna Karin Hultgård and Jacobsson, Lennart T.H. and Rudin, Anna and Mårtensson, Inga Lill and Gjertsson, Inger}},
issn = {{1478-6354}},
keywords = {{Cartilage destruction; CD21 DN B cells; Early rheumatoid arthritis}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Arthritis Research and Therapy}},
title = {{Cartilage destruction in early rheumatoid arthritis patients correlates with CD21<sup>−/low</sup> double-negative B cells}},
url = {{http://dx.doi.org/10.1186/s13075-024-03264-2}},
doi = {{10.1186/s13075-024-03264-2}},
volume = {{26}},
year = {{2024}},
}