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AB0042 Associations of plasmablasts with disease activity and therapies for rheumatoid arthritis
  1. E. Vital,
  2. A.C. Rawstron,
  3. G. Arumugakani,
  4. D. McGonagle,
  5. P. Emery
  1. Section of Musculoskeletal Disease, University of Leeds, Leeds, United Kingdom

Abstract

Background Unlike tissue resident or circulating B lineage cells, circulating plasmablasts represent B cells that have completed the affinity maturation process and are capable of antibody production. We have previously shown that this population predicts response to rituximab in RA, can predict rituximab dosing strategies and that levels at baseline and 6 months post therapy can predict response and relapse respectively [1].

Objectives To test the association of plasmablast numbers with disease activity in RA, antibody status in SLE, and non-biologic immunsuppressant use.

Methods Naive B cells, memory B cells and plasmablasts were enumerated by a flow cytometry protocol designed to optimise plasmablast detection. Scatter properties and expression of CD19, CD20, CD27, CD38 with sequential gating were used to classify B cell subsets, with exclusion markers. Samples were obtained from patients with active rheumatoid arthritis (RA) on methotrexate (n=90), leflunomide (n=15) or no therapy (n=20), patients with RA in remission (n=23), patients with active SLE (n=38), and healthy controls (n=12). The predictive value of B cell subsets for clinical (EULAR) response with adjustment for conventional DMARD and disease activity was tested in a cohort of 161 patients pooled from previous clinical trials.

Results Comparing untreated active RA and healthy controls, total and naive B cell numbers were not different, but there were significantly lower numbers of memory B cells (p=0.026) and significantly higher numbers of plasmablasts (p=0.026). Comparing patients with active SLE and healthy controls, there were significantly lower numbers of naive (p=0.036) and memory (p<0.001) B cells, and significantly higher numbers of plasmablasts (p=0.098).

In RA, remission and treatment with methotrexate or leflunomide were associated with significantly lower numbers of plasmablasts compared to untreated active RA. No significant difference was observed in naive and memory B cells between these groups.

In SLE, presence of antibodies to the extractable nuclear antigens Ro, La, Sm and ribonuclear proteins were all associated with significantly higher numbers of plasmablasts compared to SLE patients without each respective antibody.

Lastly, we performed multivariate analysis including baseline plasmablast number, 2-week and 6-week depletion of each B cell subset, age, baseline disease activity, rheumatoid factor titre, prior anti-TNF use and concomitant DMARD to predict response to rituximab in rheumatoid arthritis. Significant effects were identified for prior TNF use (p=0.009), baseline plasmablast number (p=0.015) and 2-week plasmablast depletion (with interaction between baseline and 2 week plasmablast numbers, p=0.017).

Conclusions Active B cell mediated autoimmune diseases are associated with increased numbers of plasmablasts compared to healthy controls. Their numbers are reduced with treatment with conventional immunosuppressants. These results suggest that plasmablast generation may be involved in disease pathogenesis. Plasmablasts are not directly depleted by rituximab and have previously been shown to predict worse clinical response in RA by our group and others. Our analysis shows that this effect is independent of the effect of DMARDs and baseline disease activity, and more strongly associated with response than other B cell subsets.

  1. Vital EM et al. Arthritis Rheum. 2010 May;62(5):1273-9.

Disclosure of Interest None Declared

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