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08.46 Alterations in peripheral blood b-cell subsets following conventional and tnf-inhibitor therapies in patients with early, treatment-naïve rheumatoid arthritis
  1. Lynsey Johnston1,
  2. Andy Rawstron2,
  3. Agata Burska1,
  4. Aamir Aslam1,3,
  5. Edward M Vital1,3,
  6. Maya H Buch1,3
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK
  2. 2Haematology Malignant Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Abstract

Background In rheumatoid arthritis (RA), several studies demonstrate functionally distinct peripheral B-cell subsets relate to disease duration and response to B-cell depleting rituximab therapy.1–3 Changes following treatment with tumour necrosis factor (TNF)-inhibitor (TNFi) in peripheral blood and tonsillar tissue as well as synovial tissue have been reported.4,5 We have previously noted decreased peripheral memory B-cell and increased plasmablast numbers in active RA on no disease modifying anti-rheumatic drug (DMARD) compared with healthy controls (unpublished observations). Whilst methotrexate (MTX)-induced remission was associated with lower plasmablasts, TNFi (adalimumab+etanercept)-induced remission led to high peripheral plasmablasts.

The aim of this study was to investigate further changes in peripheral B-cell subset populations with first-line conventional and TNF-inhibitor-induced suppression of inflammation.

Materials and methods Highly sensitive flow cytometry was performed on peripheral blood of 120 patients with early, treatment-naïve RA, randomised to either etanercept/MTX or MTX +/- additional conventional DMARD, switching to etanercept/MTX at 6 months if remission was not achieved.6 Preliminary baseline-week 24 findings are reported.

Results Baseline: No significant differences in absolute number of or percentage B-cell populations were observed between groups 1 and 2.

Week 0– 24 changes: ETN/MTX: Total number of B-cells increased from week 0–24, (0.1083–0.1557); specifically, significant memory cell (0.0226–0.0338, p<0.05) increase with non-significant naïve cell increase and plasmablast number decrease (0.0026–0.0021). These changes reflected significant decrease in percentage plasmablast (2.4%–1.48%); with non-significant increase in percentage memory and naïve cell.

MTX/conventional DMARD: All changes following treatment were non-significant. Numerical increase in absolute naïve (0.0952–0.0964) and memory B-cells (0.0272–0.0321); with decrease in plasmablast (0.0027–0.0012) numbers was observed. However, non-significant percentage naïve population decrease (76.88–73.78) and plasmablast (2.29–1.50); with percentage increase in memory cells (20.78–24.73) was observed.

Conclusions Initial analysis demonstrates more marked alteration in B-cell population composition following first-line ETN/MTX compared to conventional DMARD alone, with absolute increase in memory but percentage decrease in plasmablast cells. This suggests more efficient B-cell homeostasis with ETN/MTX combination in early RA (compared to established). More effective (synovial) inflammation suppression, additional role of MTX +/- etanercept also targeting lymphotoxin may underlie these observations. Planned detailed analysis will clarify the relationships further, including disease activity state and response status.

References

  1. Daien CI, et al. Arthritis Research & Therapy2014, 16:R95

  2. Vital E, et al. Arthritis Rheum2010. 62(5)

  3. Fedele AL, et al. BMC Immunology2014, 15:28

  4. Souto-Carneiro MM, et al. Arthritis Research & Therapy2009, 11:R84

  5. Anolik JH, et al. J Immunol2008, 180:688-692

  6. Dumitru RB, et al. BMC MSK2016, 17:61

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