A3.27 Effect of rituximab on different isotypes of serum immunoglobulins in patients with SLE.

BACKGROUND AND AIMS: The impact of rituximab therapy on different compartments of the immune system may inform as to the possible clinical response and also maintenance of protective immunity. We conducted a retrospective study of serum IgM, IgG and IgA in 59 patients with SLE, following the first cycle of B cell depletion therapy based on rituximab (RTX).

MATERIALS AND METHODS: Serum Ig levels (IgA, IgG and IgM) were assessed at baseline (before first infusion of RTX) and at 1, 2, 6, 9 and 12 months after the first cycle of RTX in 59 patients with SLE. Paired t-test and Spearman's rank correlation were used to analyse changes in serum Ig levels and to analyse correlations, respectively.

RESULTS: Median baseline serum IgA level was 2.9g/L, which fell by a mean 10% and 8% (p<0.05), at 1 and 2 months after RTX but were similar to baseline at 12 months. IgA levels at baseline showed a positive correlation with IgA levels at all time points (r(2)≥0.5, p<0.0001 for all). Median baseline serum IgG level was 13.9g/L, which was significantly reduced (p<0.05) (means of 10% and 20% at 1 and 2 months after RTX) but levels were similar to baseline at all other time-points. Median baseline serum IgM levels were 1.0g/L, which reduced by means of 20%, 31%, 28%, 55% and 40% at 1, 2, 6, 9, and 12 months respectively (p<0.005 for all). Serum IgG levels at 12 months either reduced (group1) or increased (group2) from baseline. There was a significant difference in baseline IgG levels between the two groups with a median level of 17.24g/l and 10.7g/l (p = 0.0005) for group 1 and 2, respectively. Baseline IgG levels positively correlated with IgG levels at all time-points (r(2) ≥ 0.6, p<0.005 for all). However, there was no difference in IgG levels at 12 months between the two groups. Whereas in patients with IgM levels <0.4g/l at 12 months, there was a significant positive correlation only between baseline IgM levels and at 2 months, but not at other time-points. There was no correlation between absolute numbers of CD19+ cells at baseline and serum Ig levels or%change in Ig levels at any time-points.

CONCLUSION: Our results reveal a disparity in changes in IgA, IgG and IgM levels following rituximab treatment in SLE. Disease-associated defects in B cell biology particularly accessory cell and T-cell interactions associated with B cell survival and class-switch may, at least in part, account for this disparity.