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

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 (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.

Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency

“…Besides B cell depletion, rituximab induced a depletion of CD4 + T cells in patients with RA, which was associated with clinical response [45]. Studies on peripheral lymphocyte subsets in rheumatic diseases such as rheumatoid arthritis, Sjögren's syndrome, SLE and spondylarthritis have identified changes both within the T and B cells and in some cases associated those changes with disease activity or with phenotypic variations [46][47][48][49][50][51]. Overall, B and T cell subset abnormalities within rheumatic diseases, their association with disease activity or particular disease subgroups and/or anti-inflammatory drugs remain to be better elucidated in larger longitudinal cohorts including in the treatment of naïve patients.…”

Th17 cell pathogenicity and plasticity in rheumatoid arthritis

“…Infiltration of inflammatory cells is a pathologic feature of RA, in addition to the hyperplasia of synovial membranes and pannus growth. RA has been investigated for over a century and many studies have indicated that various types of immune cells such as CD4 + Th cells (CD4 + T cells, Th cells), macrophages, and B cells are responsible for the pathogenesis of RA . However, the immunologic mechanism of RA is still unknown.…”

A Panoply of Rheumatological Manifestations in Patients with GATA2 Deficiency

“…An expansion of a small subset of CD38 low CD21 low B cells in patients with GATA2 deficiency was described 14 . This subset is also expanded in the peripheral blood of patients with systemic lupus erythematosus (SLE) 25 , seropositive rheumatoid arthritis (RA) 26 , and Sjögren's syndrome 27 . Further, in patients with RA, CD21 low B cells were identified as a major B cell population in synovial fluid 28 .…”