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IFN signature determines responder status on B cell depletion in rheumatoid arthritis patients
  1. S Vosslamber1,
  2. H G Raterman2,
  3. M Schreurs1,
  4. T van der Pouw Kraan3,
  5. M T Nurmohamed4,
  6. W F Lems2,
  7. B A C Dijkmans2,
  8. A Voskuyl2,
  9. C Verweij1
  1. 1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  3. 3Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
  4. 4Department of Rheumatology, Jan van Breemen Institute, Amsterdam, The Netherlands

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B cells are supposed to play an important role in rheumatoid arthritis (RA). Accordingly, rituximab, a chimeric monoclonal antibody against CD20, effectively depletes B cells ameliorates disease although a subset of patients don't respond. We aimed to identify biomarkers and biological processes underlying non-responsiveness. Therefore, the effect of rituximab on gene-expression levels in peripheral blood of responders and non-responders was studied.

RNA was isolated from 15 rituximab-treated RA patients before, 3 and 6 months after start of treatment. Gene-expression profiling was performed using Illumina HumanHT 12-vs bead chips. Clinical responder status was determined after 6 months by change in disease activity score (ΔDAS).

Pharmacogenomics revealed 16 B cell related genes that were significantly downregulated after 3 months. Subsequent analysis of expression profiles of patients ranked by increasing ΔDAS learnt that a good response (ΔDAS28 >1.2) is observed for patients with a low level of expression of a cluster of type-I interferon response genes (IRG) at baseline (p=0.065). We observed that after 3 months regulation of IRG-activity varied between patients. An increase in IRG-expression was observed for good responders (ΔDAS28 >1.2), whereas no induction or decrease was found for non-responders.

The IRG signature is associated with responder status upon B cell depletion therapy in RA.

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