Article Text

THU0496 B-Cell Subpopulations Differ in Rheumatoid Arthritis Patients with and without Autoantibodies
  1. K. Thorarinsdottir,
  2. P. Jirholt,
  3. L. Jacobsson,
  4. I.-L. Mårtensson,
  5. I. Gjertsson
  1. University of Gothenburg, Gothenburg, Sweden


Background Rheumatoid arthritis (RA) is a common, destructive and non-curable autoimmune disease that affects approximately 0.5-1% of the population of the Western world. The importance of B cells in RA has regained interest in the last decade following the discovery of highly disease-specific antibodies against citrullinated proteins (ACPA) and the success of treating RA with B-cell depleting therapy. It is known that the B cell memory compartment is altered in RA, however, the kinetics, phenotype and function of the various B cell populations are not. We, and others, have uncovered an autoreactive B cell subpopulation in both mice and RA patients, which lacks the expression of the CD21 and CD23 markers and most likely belong to the memory B cell pool (1,2).

Objectives To investigate whether different B-cell subpopulations in RA patients correlate to disease activity, erosivity, autoantibody profile and clinical response, which could provide biomarkers for treatment response or even provide new treatment targets.

Methods In a cross-sectional study, female patients with manifest RA according to ACR1987 criteria (n=30, mean age: 56 y) were stratified into two groups: with and without autoantibodies (ACPA, Rheumatic Factor and/or Anti-Nuclear Antibodies). Patients with other autoimmune diseases, rituximab treatment, cancer or infections were excluded.

In an ongoing longitudinal prospective study, a spin-off project from the Scandinavian study Nord-Star (n=800), incident RA-patients (according to ACR/EULAR 1987/2010) at our site (n=50, age and sex so far not analyzed) are randomized to head-to-head treatment with methotrexate and either a) certilizumab; b) tocilizumab; c) abatacept or d) prednisolone and assessed at diagnosis and after 1, 3, 6 and 12 months.

Clinical response (DAS28), joint erosivity (X-ray), autoantibodies and B-cells are assessed. Flow cytometry is used for the analysis of the following surface markers on leukocytes in peripheral blood: CD19, CD27, CD21, CD23, CD24, CD27, CD38, PD-1, PD-L1, IgG, IgD and IgM.

Results The crossectional study indicates a pronounced variation in B-cells lacking CD21 and CD23 (CD21-CD23-). In RA patients with autoantibodies the frequency of switched memory B cells, i.e. not expressing IgM or IgD, in the CD21-CD23- subgroup is decreased compared to patients lacking autoantibodies. In addition, the absolute number of memory B cells is decreased in patients with autoantibodies and coincides with increased joint erosivity.

The ongoing longitudinal study indicates alterations particularly in the CD21-CD23 subpopulation. The difference was most pronounced between the untreated RA patients and healthy matched controls: memory B cells were decreased at diagnosis of RA but increased with treatment, while both plasmablasts and immature B cells were increased at diagnosis but decreased with treatment.

Conclusions Our data suggest that the B cell compartment is disturbed already early in the disease and that there are differences in B-cell subpopulations between RA patients with and without autoantibodies.


  1. Keenan, R.A., de Riva, A., Martensson, I.L. et al 2008. Censoring of autoreactive b cell development by the pre-b cell receptor. Science 321:696-699.

  2. Isnardi, I., Ng, Y.S., Menard, I., Meyers, G., et al. 2010. Complement receptor 2/cd21- human naive b cells contain mostly autoreactive unresponsive clones. Blood 115:5026-5036.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2999

Statistics from

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.