Article Text

PDF
01.06 B-cell phenotype and igd-cd27- memory b cells are affected by tnf-inhibitors and tocilizumab treatment in rheumatoid arthritis
  1. Rita A Moura1,
  2. Cláudia Quaresma1,*,
  3. Ana R Vieira1,*,
  4. Maria J Gonçalves1,2,
  5. Joaquim Polido-Pereira1,2,
  6. Vasco C Romão1,2,
  7. Nádia Martins2,
  8. Helena Canhão1,2,
  9. João E Fonseca1,2
  1. 1Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  2. 2Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Portugal
  3. *Equally contributed to this study.

Abstract

Background The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA.

Materials and methods Blood samples were collected from untreated early RA (ERA) patients (<1 year of disease duration), established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA.

Results The frequency of total CD19+ B-cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B-cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B-cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab.

Conclusions In RA, treatment with either TNF-inhibitors or tocilizumab affects B-cell phenotype and the frequency of memory B-cell subpopulations in peripheral blood, particularly DN (IgD-CD27-) B-cells, but not B-cell gene expression or serum levels of CXCL13, sCD23 and BAFF, when comparing baseline with post-treatment follow up. Overall, our results may suggest that TNF-inhibitors and tocilizumab inhibit B-cell trafficking towards inflammatory sites, thus supporting activated B-cell recirculation from tissues through blood and lymphatic systems.

Keywords
  • Rheumatoid arthritis
  • B cells
  • TNF-inhibitors
  • Tocilizumab

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.