ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1623

Increased CD95 (Fas) Expression on Naive B Cells Is Associated with a Switch to Double Negative and Plasma Cells in the Peripheral Blood, and Correlates with Disease Activity in Systemic Lupus Erythematosus

Julie Ducreux1, Séverine Nieuwland2, Frédéric A. Houssiau1 and Bernard R. Lauwerys1, 1Institut de Recherche Expérimentale et Clinique, Pôle de Maladies Rhumatismales, Université catholique de Louvain, Brussels, Belgium, 2Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales, Université catholique de Louvain, Brussels, Belgium

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Autoimmune Disease Transition, Disease Subsets and Prediction of Flares, Cytokines and Autoantibodies

Session Type: Abstract Submissions (ACR)

Background/Purpose: systemic lupus erythematosus (SLE) is characterized by a break of tolerance to autoantigens, and polyclonal activation of B cells. We performed multicolor flow cytometry analyses of B cell subsets in SLE patients and controls, in order to increase our understanding of the B cell activation steps characteristic of the disease.

Methods: PBMC from 16 SLE patients and 5 controls were analyzed using the following flow cytometry markers : CD5, IgD, CD27, CD20, CD19, CD38, CD95 and intracellular survivin, and their control isotypes. The data were acquired using a BD FacsCantoII and analyzed using FlowJo software. Serum C3 concentrations were retrieved from the medical records of the patients.

Results: SLE patients had significantly less CD19+CD20+IgD+CD27- naive B cells compared to controls (40.5 ± 30.7 versus 70.4 ± 8.5 % of total B cells, p = 0.048). By contrast, proportions of CD19+CD20+IgD-CD27- double negative (11.6 ± 8.8 versus 4.2 ± 1.6 %, p = 0.029) and CD19+CD20-CD38+ plasma cells (11.5 ± 18,4 versus 1.5 ± 1.0 %, p = 0.015) were significantly higher in SLE patients compared to controls. Proportions of CD19+CD20+IgD-CD27+ conventional memory B cells were also higher in SLE patients, but the difference was not significant (24.5 ± 18.7 versus 11.9 ± 4.4 %, p = 0.15).

Percentage of CD95 (Fas) positive cells was significantly higher in SLE naive (24.5 ± 17,4 versus 2.4 ± 1.3 %, p = 0.001), but also in double negative B cells compared to controls. Almost all SLE and control plasma cells expressed CD95. Strikingly, expression of CD95 on naive B cells correlated negatively with the proportion of naive B cells themselves (r = -0.50, p = 0.022), and positively with the proportions of double negative (r = 0.46, p = 0.034) and plasma cells (r = 0.57, p = 0.007).

In all B cell subsets, expression of CD95 displayed a significant positive correlation with intracellular expression of survivin (r = 0.63, p = 0.002), a cell proliferation and anti-apoptotic marker. Finally, we observed a significant negative correlation between both CD95 (r = -0.53, p = 0.036) or survivin (r = -0.50, p = 0.048) expression in naive B cells and serum C3.

Conclusion: CD95 expression on naive B cells is associated with a switch to double negative and plasma cells in the peripheral blood of SLE patients. The positive correlation between CD95 and survivin expression in SLE B cell subsets confirms that CD95 is a marker of B cell activation in SLE. Activation (CD95 and survivin expression) of naive B cells correlates with disease activity. Further studies on additional cross-sectional and longitudinal samples are ongoing.

Disclosure:

J. Ducreux,
None;

S. Nieuwland,
None;

F. A. Houssiau,
None;

B. R. Lauwerys,
None.

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