Article Text

PDF

A2.12 Increased CXCR5 B cell expression, CXCL13 and SCD23 serum levels in untreated early rheumatoid arthritis patients support B cell activation since the initial phase of the disease
  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
  3. *C. Quaresma and A. R. Vieira Equally Contributed for this Work

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, but few studies have been performed in untreated early RA patients. Therefore, the main goal of this study was to characterise B-cell phenotype and B-cell gene expression levels since early RA onset in comparison with the chronic phase of the disease.

Materials and methods Blood samples were collected from untreated early RA (ERA) patients (<1 year of disease duration), established RA patients under methotrexate treatment and age and sex-matched 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 patients’ groups, but established RA had significantly increased frequencies of double negative (IgD-CD27-) B-cells in comparison with controls. CXCR5 B-cell expression was significantly increased in both ERA and established RA in comparison with controls, but no significant differences were observed in BAFF-R, TACI, BCMA, CD69, CD86, HLA-DR, TLR9, CD95, IgM and CD5 B-cell expression between all groups analysed. Furthermore, alterations in B-cell gene expression levels were found in BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M in ERA and established RA patients when compared to controls, but no significant differences were detected in AID, BCMA, CXCR5, TLR7 and TLR10 B-cell gene expression between all groups. In addition, CXCL13 and sCD23, but not BAFF serum levels, were significantly increased since early RA.

Conclusions CXCR5 B-cell expression and CXCL13 serum levels are significantly increased in untreated early RA (<1 year of disease duration) and established RA patients when compared to controls, which supports B-cell activation and recruitment to inflammatory sites since early disease onset. Alterations in B-cell gene expression levels increase with disease progression, particularly in BAFF- and toll-like receptors. The augmented sCD23 serum levels detected in ERA patients suggest that B-cell maturation occurs from early RA onset.

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.