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.
Dass et al Arthritis Rheum. 2008 Oct;58(10):2993-9.
Disclosure of Interest None Declared
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