Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
CD23 is the low-affinity receptor for IgE (FceRII). The soluble form, sCD23 is released into the circulation and in vitro this is consistent with cleavage from naive B cells and expression of CD27 (a marker of memory B cells). BAFF (B cell activation factor) is a survival factor for predominantly naive B cells and is involved in B-cell proliferation, plasma cell differentiation and, with APRIL, also class switching. High levels of sCD23 and of BAFF can be present in sera from patients with Systemic Lupus Erythematosus (SLE) and other autoimmune diseases. The inter-relation between sCD23 and BAFF has not been studied in relation to Rituximab (RTX) treatment.
Aim To investigate the relationship between sCD23 and serum BAFF at baseline and after RTX in patients with SLE.
Methods
Twenty eight patients with SLE (diagnosed according to the 1982 ACR revised criteria) were studied before B cell depletion therapy (BCDT) based on RTX and 18 SLE patients after RTX treatment. Twenty eight healthy controls (HC) were also included. Serum sCD23 (normal range given by manufacturers; 1235-5024pg/ml;) and BAFF levels were determined using ELISA. Results were analysed in relation with C3 level, anti-ds DNA titer, IgA, IgG, IgM level and CD19+ B cell count.
Results
Before RTX, sCD23 levels were positively correlated with serum BAFF (p=0.05, r2 0.47). There was no correlation between sCD23 levels with C3, anti ds-DNA, total serum IgA, IgG or IgM. In HC, sCD23 levels did not correlate with serum BAFF (r2 =0.23: p=0.10). Further, in patients with levels of sCD23 above the normal range (>5024pg/ml; n=7) median BAFF levels were significantly higher than those with sCD23 within normal limits (n=21) (median BAFF levels: 3.37 and 1.35 ng/ml respectively).
In the 15/28 SLE patients with active disease (BILAG score), there was an even stronger correlation between sCD23 levels and serum BAFF (r2 =0.56, p=0.001) but no correlation between sCD23 and anti-ds-DNA, IgA, IgG or IgM levels. There was a tendency towards lower C3 values in those patients with sCD23 above the normal range. Median BAFF levels were significantly higher in this group (n=6; 5.75 ng/ml) compared to patients with sCD23 within the normal range (n=9; median BAFF: 1.25 ng/ml) (p=0.001).
After RTX, in 10 patients from whom serial samples were available, sCD23 decreased by a median of 39% at 3 months and 56% at 3-6 months consistent with removal of the majority of circulating B cells but levels did not fall below the normal range.
Conclusion
In vitro, the addition of BAFF to B cell cultures stimulated through either Toll-like receptors and the B-cell receptor significantly increases sCD23 cleavage from the B cell surface. Before RTX, serum BAFF levels were related to levels of sCD23 above the normal range in patients with SLE, most markedly in patients with active disease. Serum BAFF is raised in some SLE patients due to changes in availability of BAFF-R, B-cell lymphopenia, BAFF production, or induction by interferons. Germinal center structure is also disturbed in SLE, possibly related to high BAFF levels, which may result in decreased stringency for naïve B cell differentiation into memory phenotype, accompanied by release of sCD23. Levels of sCD23 may be a useful measure of B cell maturation in vivo.
Disclosure:
L. Heretiu,
None;
M. J. Leandro,
None;
V. Reddy,
None;
D. A. Isenberg,
None;
G. Cambridge,
None.
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