Article Text

FRI0042 BAFF-R expression in naÏve CD5+IGM+ B cells in rheumatoid arthritis patients repopulating after rituximab
  1. E Becerra1,2,
  2. I de la Torre2,
  3. MJ Leandro2,
  4. G Cambridge2
  1. 1Rheumatology, Hospital universitario de Torrevieja, Alicante, Spain
  2. 2Rheumatology, University College London, London, United Kingdom


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.

Table 1

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

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.