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AB0038 Differential Outcome of B Cell Depletion in Patients with Anca-Associated Vasculitis (AAV) Compared to Patients with Systemic Lupus Erythematosus (SLE)
  1. U. Saunders1,
  2. P. Willeke1,
  3. H. Becker1,
  4. T. Fassbinder1,
  5. E. Jung1,
  6. E. Mickholz1,
  7. B. Schlüter2,
  8. A.M. Jacobi1
  1. 1Division of Rheumatology and Clinical Immunology/Internal Medicine D
  2. 2Center of Laboratory Medicine, University Hospital Münster, Münster, Germany

Abstract

Background B lymphocytes play a fundamental role in adaptive immune responses against pathogens. However, self-reactive memory B cells and long-lived plasma cells are a hard-to-hit target in patients with autoimmune diseases. Clinical trials with the B cell depleting CD20-antibody rituximab (RTX) revealed mixed results, with a benefit in patients with rheumatoid arthritis (RA) or AAV but less consistent results in patients with SLE.

Objectives To investigate the influence of B cell depletion by RTX on circulating B cells from patients with AAV and SLE.

Methods Peripheral blood samples of 12 AAV and 9 SLE patients were obtained prior and 8-12 weeks post RTX treatment and B lymphocyte subsets were analyzed by multiparameter flow cytometry. In addition, changes in immunoglobulin, free light chain (FLC), autoantibody, and BAFF serum levels were determined at both time points.

Results AAV patients displayed a significant depletion of all circulating B cell subsets 2-3 months post RTX. In contrast, 2 SLE patients had still detectable numbers of peripheral CD27++CD38++HLA-DRhigh plasmablasts, CD27++CD38++HLA-DRlow plasma cells and CD27+IgD memory B cells 8-12 weeks after the RTX infusions (Table 1). BAFF serum levels increased by 70% in AAV (p<0.03) and 45% in SLE patients. IgA, IgG, FLC, and autoantibody levels declined but did not drop significantly during the first weeks after B cell depletion in both patient groups. However, IgM showed a significant decrease in patients with AAV (p<0.04).

Table 1.

Absolute numbers of peripheral B cell subsets pre and post B cell depleting therapy

Conclusions In contrast to patients with SLE, B cell depleting therapy goes along with a significant decline of all B cell subsets in patients with AAV.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2226

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