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CD21−/low B cells associate with joint damage in rheumatoid arthritis patients

Thorarinsdottir, Katrin ; Camponeschi, Alessandro ; Jonsson, Charlotte ; Granhagen Önnheim, Karin ; Nilsson, Jenny ; Forslind, Kristina LU ; Visentini, Marcella ; Jacobsson, Lennart ; Mårtensson, Inga Lill and Gjertsson, Inger (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 CD27IgD 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 CD27IgD, 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 CD27IgD subset of CD21−/low B cells may mediate joint destruction in patients with ACPA+/RF+ RA.

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organization
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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
2020-08-12 08:47:15
@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 &lt; 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},
  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},
}