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A3.27 Effect of rituximab on different isotypes of serum immunoglobulins in patients with SLE
  1. Venkat Reddy1,
  2. Lina Martinez2,
  3. David Isenberg1,
  4. Geraldine Cambridge1,
  5. Maria Leandro1
  1. 1Centre for Rheumatology, University College London, 424, The Rayne Building, 4th Floor, 5 University Street, London, UK WC1E 6JF
  2. 2Hospital General Universitario, Gregorio Marañón, C/ Doctor Esquerdo, 46, 28007 Madrid, Spain

Abstract

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 (r2≥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 (r2 ≥ 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.

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