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.
F. A. Houssiau,
B. R. Lauwerys,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/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-erythem/