Article Text

PDF
AB0027 B-Cell Activating Factor (BAFF) Binding Receptors (BBR) on B Cells: Characterization in Patients with Rheumatoid Arthritis (RA) Receiving Biological Therapies: Anti-TNF, Anti-Il6r and Anti-Ctla4: A Longitudinal Study
  1. D. Hernández Flόrez1,
  2. L. Valor1,
  3. I. de la Torre1,
  4. A. Gallego2,
  5. E. Chamizo2,
  6. T. del Río1,
  7. L. Martinez1,
  8. C. Gonzalez1,
  9. J. Lopez-Longo1,
  10. I. Monteagudo1,
  11. E. Naredo1,
  12. M. Montoro1,
  13. M. Salvat1,
  14. L. Carreño Perez1
  1. 1Rheumatology, Hospital General Universitario Gregorio Marañόn, Madrid
  2. 2Rheumatology, Hospital Clínico, Mérida, Spain

Abstract

Background The treatment of rheumatoid arthritis (RA) has improved in the last years because of both: an increased understanding of its pathogenesis and the use of biological therapies. It is well known that B cells play a pivotal role in the development of autoimmune processes mainly as a precursor of antibody-secreting cells and also as antigen-presenting cells (APC). The development, survival and maturation of B-cells depend among others factors on specific membrane receptors. In this longitudinal study we have evaluated BAFF-Binding Receptors [BBR: BAFF-R (B-cell activating factor), TACI (transmembrane activator and calcium-modulating and cyclophilin ligand interactor), BCMA (B-cell maturation antigen)] and the activation marker CD86 expression on B-cells in response to three different therapeutic targets, anti-TNF (tumor necrosis factor): [infliximab (IFX), adalimumab (ADA), etanercept (ETA)]; anti-IL6R (Interleukin-6 receptor): tocilizumab (TCZ) and the anti-CTLA4 (Cytotoxic T-Lymphocyte Antigen 4): abatacept (ABC).

Objectives To investigate the possible role of biological therapies in B-cells phenotype changes and therefore in their survival/maturation process in patients with RA.

Methods 39 patients diagnosed with RA and naive to biological therapies, started treatment with ADA (n=7), ETN (n=9) IFX (n=3), TCZ (n=15) and ABC (n=5). They were assesed at baseline and every 4 month for one year. Peripheral whole blood was stained with conjugated monoclonal antibodies directed to CD19, CD27, IgD, CD38, BAFF-R, BCMA, TACI and CD86 and then evaluated by multiparametric flow cytometry. The patients were classified according to the therapeutic target: ADA+ETN+IFX (anti-TNF), TCZ (anti-IL6R) and ABC (anti-CTL4).

Results We found decreased percentages (%) of memory B-cells (CD19+/CD27+) and an inversely proportional increase of naïve B-cells (CD19+/CD27−) in the groups ABC vs. anti-TNF and TCZ. Regarding the B-cell subsets, % of memory resting B-cells (CD19+/IgD+/CD38−) were lower in all three groups being more marked in the ABC group, whereas % of post-germinal center B-cells (CD19+/IgD−/CD38+) were lower in anti-TNF and ABC vs. TCZ. Regarding the BBR expression on memory B-cells, we found a decreased TACI expression in TCZ vs. anti-TNF and ABC, and also a decreased CD86+ expression in ABC vs. anti-TNF and TCZ.

Conclusions In this exploratory study, the regulatory effect (TACI) on the B-cell phenotype and CD86 expression was more evident in the TCZ and ABC groups. These changes might be explained by two different key pathways for immune-regulation, the effect of cytokines and the cell-cell interaction process. Our data suggested that the monitoring of B-cells may be useful to further understand the role of specific B-cell receptors in the pathogenesis of RA and its association with clinical response to biological therapies.

Disclosure of Interest D. Hernández Flόrez: None declared, L. Valor: None declared, I. de la Torre: None declared, A. Gallego: None declared, E. Chamizo: None declared, T. del Río: None declared, L. Martinez: None declared, C. Gonzalez: None declared, J. Lopez-Longo: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, E. Naredo Grant/research support: UCB and MSD, Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, M. Montoro: None declared, M. Salvat: None declared, L. Carreño Perez: None declared

DOI 10.1136/annrheumdis-2014-eular.3191

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.