Article Text

PDF
A1.12 B-cell markers expression is affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis
  1. RA Moura1,
  2. C Quaresma1,*,
  3. Ar Vieira1,
  4. MJ Gonçalves1,2,
  5. J Polido-Pereira1,2,
  6. V Romão1,2,
  7. N Martins2,
  8. H Canhão1,2,
  9. JE Fonseca1,2
  1. 1Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal
  2. 2Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Portugal

Abstract

Background and objectives B cells play several important roles in rheumatoid arthritis (RA) pathogenesis, namely through autoantibody production, antigen presentation and T cell activation. The use of immunosuppressive drugs such as TNF-inhibitors and/or Il-6 receptor antagonist, tocilizumab, in RA might affect the circulating numbers of B cells and their activation state. The main goal of this work was to study the effect of TNF-inhibitors and tocilizumab on B cell phenotype and gene expression before and after treatment.

Materials and methods Blood samples were collected from established RA patients treated with TNF-inhibitors (n = 10) and tocilizumab (n = 9) before and after treatment, and from healthy donors (n = 15). B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed by real-time PCR on isolated B-cells.

Results The frequency of circulating B cell subpopulations was similar between controls and established RA patients irrespective of treatment. The mean fluorescence intensity (MFI) of TACI, CXCR5 and HLA-DR expressed on CD19+B-cells was significantly increased in TNF-treated patients when compared to controls. A significant decrease of CD86 and increase of CD95 MFI was observed in CD19+B-cells after TNF treatment. In tocilizumab-treated patients, HLA-DR and TLR9 MFI were significantly increased in CD19+B-cells when compared to controls. No significant differences were observed in BAFF-R, BCMA, IgM and CD69 MFI in both groups of patients compared to controls. BAFF-R, Bcl-2, β2-microglobulin, FcgR2A, TLR7 and TLR10 gene expression were significantly increased after treatment with TNF and/or tocilizumab in comparison with controls, but no significant differences were observed when comparing baseline and follow-ups.

Conclusions In RA, the use of TNF-inhibitors and/or tocilizumab treatment affects B-cell phenotype in circulation, but the effect of these drugs on B-cell gene expression is less evident. The decreased levels of CD86 expression and increased CD95 MFI on B-cells after TNF treatment support an inhibition of B-cell activation. Our results suggest that TNF-inhibitors and tocilizumab help to reduce B-cell infiltration in the joints and these activated B-cells express higher HLA-DR and CXCR5 levels in circulation.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.