METHODS: Using the Johns Hopkins arthritis cohort and biorepository, we contrasted serum protein levels of B-cell factors involved in homing (CXCL-10, CXCL-11, CXCL-12, CXCL-13 and CCL-19), activation (CD40, CD40L) and survival (BAFF, APRIL, TACI and BCMA) in healthy controls and RA patients with and without history of infections. We excluded RA patients receiving steroids, anti-B cell therapy, non-TNF inhibitors biologics, azathioprine, leflunomide, sulfasalazine or >1 disease-modifying anti-rheumatic drug. Serum B-cell factors were quantified by multiplex immunoassays.
RESULTS: We included 10 healthy controls and 24 adult RA patients (aged 24-64 years) sub-divided into those with (n=7) and those without infections (n=17) within 2 years of enrollment. We identified that: (1) protein levels of BCMA, APRIL, CD40 and CD40L were significantly decreased in RA patients relative to healthy controls; and (2) RA patients with history of infections had significantly lower BCMA levels compared with their non-infectious RA counterparts (p<0.05).
CONCLUSIONS: Our study using soluble serum B-cell markers suggest that there are alterations in B-cell activation and survival in RA patients, and that this may be linked to increased risk of infections. Further delineating the link between B-cell function and RA outcomes may optimize disease subsetting and provide novel insights in RA pathogenesis including the individual susceptibility to infections.