FRI0042 BAFF-R expression in naÏve CD5+IGM+ B cells in rheumatoid arthritis patients repopulating after rituximab
Authors: E Becerra, I de la Torre, MJ Leandro, G Cambridge
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> 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. <h3>Objectives</h3> 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 (&gt;4 months post-B cell return). <h3>Methods</h3> 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. <h3>Results</h3> %CD5+IgM+B cells, but not absolute numbers, were significantly higher in post-RTX early relapsers compared to HC (p&lt;0.01), pre-RTX patients (p&lt;0.001) and post-RTX later relapsers (p&lt;0.01). There was a strong inverse correlation between %CD5+IgM+B cells and time after B cell return (r<sup>2</sup>=0.88, p&lt;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&lt;0.01). BAFF-R+ expression increased with time after B cell return, both % (r<sup>2</sup>=0.47, p&lt;0.002) and MFI (r<sup>2</sup>=0.76, p&lt;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&lt;0.05 compared to later relapsers). There was a significant inverse correlation between BAFF levels and % (r<sup>2</sup>=0.51, p&lt;0.01) and MFI (r<sup>2</sup>=0.4, p&lt;0.05) BAFF-R+ expression. <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> None declared