CD27^-CD38^lowCD21^low B-Cells Are Increased in Axial Spondyloarthritis

B-cells have received little attention in axial spondyloarthritis (axSpA) and for this reason their role in pathogenesis remains unclear. However, there are indications that B-cells may be involved in the disease process. Our objective was to obtain insights into the composition of the peripheral B-cell compartment of axSpA patients compared to healthy donors (HD) and patients with primary Sjögren's syndrome (pSS), a typical B-cell-associated autoimmune disease. Special emphasis was given to CD27-negative B-cells expressing low levels of CD21 (CD21^low B-cells), since this subset is implicated in autoimmune diseases with strong involvement of B-cells. Transitional B-cells (CD38^hi) were excluded from the analysis of the CD27^-CD21^low B-cell compartment. This study included 45 axSpA patients, 20 pSS patients and 30 HDs. Intriguingly, compared to HDs the frequency of CD27^-CD38^lowCD21^low B-cells was significantly elevated in both axSpA and pSS patients (P<0.0001 for both comparisons). The frequency of CD27^-CD38^lowCD21^low B-cells expressing the activation-induced immune markers T-bet and CD11c was decreased in axSpA patients compared to HDs. A higher proportion of CD27^-CD38^lowCD21^low B-cells expressed the chemokine receptor CXCR3 in axSpA compared to HDs, suggestive for active involvement of these cells in an inflammatory process. The frequency of CD27^-CD38^lowCD21^low B-cells in axSpA patients correlated positively with age and erythrocyte sedimentation rate. Furthermore, axSpA patients with extra-skeletal manifestations (ESM) showed increased frequencies of CD27^-CD38^lowCD21^low B-cells compared to patients without ESM. In conclusion, our findings are suggestive of active B-cell involvement in the pathogenesis of axSpA, against prevailing dogma.