Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


The Levels of Memory B-Cells with a Plasmablast-Like Phenotype Are Associated with Response to Anti-CD20 Treatment in Rheumatoid Arthritis.

Arumugakani1,  Gururaj, Rawstron2,  Andrew, Tooze1,  Reuben, Emery3,  Paul, McGonagle4,  Dennis

University of Leeds, Leeds, United Kingdom
NIHR Leeds Biomedical Research Unit, University of Leeds and Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
Leeds Institute of Molecular Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK, Leeds, United Kingdom
University of Leeds and Leeds Teaching Hospitals, Leeds, United Kingdom

Background/Purpose:

The advent of B-cell depletion therapy has significantly improved outcome of various autoimmune conditions including Rheumatoid Arthritis (RA), Lupus, Wegner's etc. The extent of B-cell depletion determined by high sensitivity flow cytometry is a key predictor of response and outcome. The pattern of B-cell reconstitution also appears to be important as clinical relapse does not occur in individuals with sustained B-cell depletion, and recovery of plasmablasts in the absence of other B-cell subsets predicts imminent relapse. Individuals with recovery of multiple B-cell subsets have a variable clinical course but those with a high proportion of memory cells within the reconstituting B-cell pool may have an increased risk of relapse. (Dass et al Arthritis Rheum. 2008 Oct;58(10):2993–9) The aim of this study was to identify the characteristics of B-cell subsets which contribute to relapse.

Methods:

79 samples from patients with autoimmune disorders and 28 disease controls were analysed by 10-parameter flow cytometry. An antibody backbone of CD19 and CD20 CD27, and CD38 were used to identify naïve,B-cells memory B-cells and plasmablasts in the backbone to define the initial subsets. 34 additional surface markers known to be expressed by B-cells were evaluated on selected RA cases and controls to identify the most informative subsets. Final assessment of the B-cell subset distribution was performed on 7 individuals prior to first anti-CD20 treatment and 6 individuals with relapsed disease prior to re-treatment.

Results:

An iterative approach was used to select markers for further investigation, with an initial stage to detect markers with heterogeneous expression followed by further stages to identify combinations of markers which were complementary in the delineation of different B-cell subsets. Distinct populations could be identified by differential expression of 9 markers, 5/9 of these identified a population of CD38-negative memory B-cells which were otherwise phenotypically similar to plasmablasts. The proportions of these plasmablast-like memory B-cells were relatively low in control cases (median 18% of total memory B-cells, range 7–29%) but were more prevalent in rheumatoid cases prior to anti-CD20 treatment (median 26% of total memory B-cells, range 20–52%) although this difference did not reach statistical significance (Mann Whitney P=0.22). Individuals with relapsed disease requiring re-treatment had variable numbers of naïve B-cells but showed a highly significant increase in the proportion of plasmablast-like memory B-cells (median 55%, range 39–65%, Mann-Whitney P=0.007).

Conclusion:

Extensive analysis of B-cell subsets in rheumatoid patients demonstrates heavy skewing of the memory B-cell pool in individuals relapsing after anti-CD20 treatment. Poor or unsustained response to anti-CD20 treatment is associated with the persistence and/or skewed reconstitution by both plasmablasts and plasmablast-like memory B-cells during and after anti-CD20 treatment.

To cite this abstract, please use the following information:
Arumugakani, Gururaj, Rawstron, Andrew, Tooze, Reuben, Emery, Paul, McGonagle, Dennis; The Levels of Memory B-Cells with a Plasmablast-Like Phenotype Are Associated with Response to Anti-CD20 Treatment in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1734
DOI:

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