Background Serum levels of B cell activating factor (BAFF) rise following Rituximab (RTX) therapy in patients with Rheumatoid arthritis (RA). CD5+IgM+B cells are present within transitional and naïve B cell subsets and their increased production or accumulation is associated with some autoimmune diseases. Previous studies have shown that BAFF does not enhance their survival compared with CD5- naïve B cells, suggesting that signalling pathways are important in promoting their survival.
Objectives To determine serum BAFF levels and BAFF-receptor (BAFF-R) expression in CD5+IgM+B cells in healthy controls (HC), RTX-naïve RA patients (pre-RTX), and relapsing at different time points after peripheral B cell repopulation post-RTX treatment, divided into 2 groups: early relapsers (0–3 months post-B cell return) and later relapsers (>4 months post-B cell return).
Methods Immunophenotyping of peripheral blood mononuclear cells was used to determine %CD5+IgM+B cells and BAFF-R (% and expression, mean fluorescence intensity (MFI)) in 5 HC, 13 pre-RTX and 12 post-RTX RA patients. Results were analyzed with respect to timing of relapse after peripheral B cell return (≥5 B cells/μL) and serum BAFF levels.
Results %CD5+IgM+B cells, but not absolute numbers, were significantly higher in post-RTX early relapsers compared to HC (p<0.01), pre-RTX patients (p<0.001) and post-RTX later relapsers (p<0.01). There was a strong inverse correlation between %CD5+IgM+B cells and time after B cell return (r2=0.88, p<0.0001). BAFF-R+ expression was significantly lower in both post-RTX groups compared to HC and pre-RTX patients; early relapsers showed the lowest % and MFI BAFF-R+ expression, compared with later relapsers (p<0.01). BAFF-R+ expression increased with time after B cell return, both % (r2=0.47, p<0.002) and MFI (r2=0.76, p<0.0004). BAFF levels were significantly higher in both post-RTX groups compared to HC and pre-RTX patients, with the highest BAFF levels in early relapsers (p<0.05 compared to later relapsers). There was a significant inverse correlation between BAFF levels and % (r2=0.51, p<0.01) and MFI (r2=0.4, p<0.05) BAFF-R+ expression.
Conclusions Early relapsers show increased %CD5+IgM+ naïve B cells, and decreased BAFF-R expression, similar to ontogeny and what is seen in cord blood B cells. Whether the increased numbers of CD5+ naïve cells were contributing to relapse was not determined but they have the capacity to rapidly mature into autoantibody producing plasma cells, independent of the BAFF/BAFFR system. BAFF-R expression was found to increase with time after B cell return, again mirroring ontogeny with a later relapse showing more normalized BAFF/BAFF-R levels, suggesting their mechanism of relapse may follow a more conventional B cell differentiation pathway.
Disclosure of Interest None declared