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THU0088 Abnormal memory B-cell reconstitution following anti-CD20 therapy for autoimmune diseases predicts clinical relapse
  1. G. Arumugakani1,
  2. A. Rawstron2,
  3. R. Tooze3,
  4. A. Cherukuri4,
  5. A. Varghese5,
  6. E. Vital1,
  7. P. Emery6,
  8. D. McGonagle1,6
  1. 1Section of Musculoskeletal Diseases, University of Leeds
  2. 2HMDS, Leeds Teaching Hospitals NHS Trust
  3. 3Experimental Haematology, University of Leeds
  4. 4Renal Medicine
  5. 5Haematology
  6. 6Rheumatology, Nihr-Lmbru, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Abstract

Background The advent of anti-CD20 therapy has significantly improved the management of various autoimmune conditions including rheumatoid arthritis (RA). The persistence of B-cells and/or plasmablasts in the immediate post-therapeutic phase (2 weeks) by highly sensitive flow cytometry has been shown to predict poor clinical response (1). However in patients with complete depletion, the return of clinical symptoms post B-cell reconstitution is variable, although clinical relapse is rare in the absence of return of B-lineage cells.

Objectives To establish the reconstitution pattern of B-cells post anti-CD20 therapy in the phase prior to clinical relapse.

Methods 79 samples from autoimmune patients and 36 disease controls were evaluated by 10-parameter flow cytometry. Scatter properties and surface expression of CD19, CD20, CD27 and CD38 was used to classify the B-lineage cells into transitional, naïve, memory B-cells and plasmablasts. Further analysis of 34 different surface markers on selected RA patients and controls was used to identify the 4 most informative markers that might help to predict disease relapse.

Results We were able to classify the memory B-cells into 16 different subsets using the 4 markers identified as above. We identified a subset with plasmablast like phenotype (CD24Lo CD84Lo CD95Hi similar to plasmablasts and CD19, CD20 & CD38 expression levels similar to memory B-cells), which constituted a higher proportion of memory B-cells and was the dominant subtype in the majority of RA patients relapsing post anti-CD20 therapy (14/18) compared to controls (2/10). The dominance of this subset was not seen in patients with Rituximab-naive activeRA (0/22) and only in 1 patient during remission (1/9) with different biologics/DMARDs. This abnormal reconstitution pattern was not seen in patients treated with Rituximab for B-cell lymphomas (0/4) or following pre-renal transplant Campath (Anti-CD52) conditioning (0/4). The samples from lymphoma patients in remission were collected 12-18 months since the last Rituximab dose and 3-6 months post-therapy in case of Campath.

Conclusions The abnormal reconstitution of memory B-cell subsets is associated with clinical relapse following anti-CD20 therapy for RA and is likely to be related to the disease process rather than the direct effect of B-cell depletion. The patients with such altered memory B-cell reconstitution might benefit from early re-treatment.

  1. Dass et al Arthritis Rheum. 2008 Oct;58(10):2993-9.

Disclosure of Interest None Declared

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