CD21−/low B cells associate with joint damage in rheumatoid arthritis patients
(2019) In Scandinavian Journal of Immunology 90(2).- Abstract
Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21−/low B cells). In this study, we sought to determine whether there was any correlation between CD21−/low B cells and clinical outcome in patients with established RA, either ACPA+/RF+ (n = 27) or ACPA−/RF− (n = 10). Healthy donors... (More)
Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21−/low B cells). In this study, we sought to determine whether there was any correlation between CD21−/low B cells and clinical outcome in patients with established RA, either ACPA+/RF+ (n = 27) or ACPA−/RF− (n = 10). Healthy donors (n = 17) were included as controls. The proportion of the CD21−/low CD27−IgD− memory B cell subset in peripheral blood (PB) was significantly increased in ACPA+/RF+ RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r = 0.57, P < 0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21−/low cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21−/low, approximately 40% of that population was CD27−IgD−, and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor κB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27−IgD− subset of CD21−/low B cells may mediate joint destruction in patients with ACPA+/RF+ RA.
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- author
- Thorarinsdottir, Katrin ; Camponeschi, Alessandro ; Jonsson, Charlotte ; Granhagen Önnheim, Karin ; Nilsson, Jenny ; Forslind, Kristina LU ; Visentini, Marcella ; Jacobsson, Lennart ; Mårtensson, Inga Lill and Gjertsson, Inger
- organization
- publishing date
- 2019-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CD21 B cells, joint destruction, rheumatoid arthritis
- in
- Scandinavian Journal of Immunology
- volume
- 90
- issue
- 2
- article number
- e12792
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:31141193
- scopus:85067875496
- ISSN
- 0300-9475
- DOI
- 10.1111/sji.12792
- language
- English
- LU publication?
- yes
- id
- 5d38a60e-df0d-47fb-916c-db65d5a697c7
- date added to LUP
- 2019-07-08 10:46:48
- date last changed
- 2024-03-03 20:02:32
@article{5d38a60e-df0d-47fb-916c-db65d5a697c7,
abstract = {{<p>Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21<sup>−/low</sup> B cells). In this study, we sought to determine whether there was any correlation between CD21<sup>−/low</sup> B cells and clinical outcome in patients with established RA, either ACPA<sup>+</sup>/RF<sup>+</sup> (n = 27) or ACPA<sup>−</sup>/RF<sup>−</sup> (n = 10). Healthy donors (n = 17) were included as controls. The proportion of the CD21<sup>−/low</sup> CD27<sup>−</sup>IgD<sup>−</sup> memory B cell subset in peripheral blood (PB) was significantly increased in ACPA<sup>+</sup>/RF<sup>+</sup> RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r = 0.57, P < 0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21<sup>−/low</sup> cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21<sup>−/low</sup>, approximately 40% of that population was CD27<sup>−</sup>IgD<sup>−</sup>, and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor κB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27<sup>−</sup>IgD<sup>−</sup> subset of CD21<sup>−/low</sup> B cells may mediate joint destruction in patients with ACPA<sup>+</sup>/RF<sup>+</sup> RA.</p>}},
author = {{Thorarinsdottir, Katrin and Camponeschi, Alessandro and Jonsson, Charlotte and Granhagen Önnheim, Karin and Nilsson, Jenny and Forslind, Kristina and Visentini, Marcella and Jacobsson, Lennart and Mårtensson, Inga Lill and Gjertsson, Inger}},
issn = {{0300-9475}},
keywords = {{CD21 B cells; joint destruction; rheumatoid arthritis}},
language = {{eng}},
number = {{2}},
publisher = {{Wiley-Blackwell}},
series = {{Scandinavian Journal of Immunology}},
title = {{CD21<sup>−/low</sup> B cells associate with joint damage in rheumatoid arthritis patients}},
url = {{http://dx.doi.org/10.1111/sji.12792}},
doi = {{10.1111/sji.12792}},
volume = {{90}},
year = {{2019}},
}