Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Recently, it has been demonstrated that a subset of T cells expresses the B-cell marker CD20. It has been postulated that in rheumatoid arthritis (RA) and multiple sclerosis (MS) the effect of rituximab (RTX), an antibody against this molecule, is partly due to the depletion of this T cell subset. Interestingly, nothing is known about CD20+T cells in another autoimmune disease that is effectively treated by RTX, viz.systemic sclerosis (SSc).
The aim of our study was to determine the frequency of CD20+ T cells and further characterize this specific subpopulation in SSc.
Methods: Peripheral blood mononuclear cells from healthy controls (HC; n=10), SSc patients treated with RTX (SSc+R; 500mg for 2x, every 3 month; n=16) or not treated with RTX (SSc-R; n=11) were characterized by flow cytometry for the surface expression of T cell specific markers as well as the production of different cytokines, i.e. TNFα, IFNγ, IL-17, after stimulation with PMA and ionomycin. In addition, apoptosis was analyzed before and after heat induction (65 °C for 5 min).
Results: SSc patients had significantly less CD20+ T cells compared to HC, independent of RTX-therapy. Thus, in SSc-R the frequency of CD20+T cells was 1,63 ± 0,32% (mean ± SE), in SSc+R 0.11% ± 0.09% and in HC 2.89% ± 1.5% (p<0.023 and p<0.001; respectively).
RTX therapy predominantely eliminated the CD8+CD20+ T cells. The ratio of CD4/8 in CD20+T cells of SSc before RTX was 0.6 similar to HC and increased during RTX to 2.1 (p<0.001).
In SSc patients, as well as in HC, the CD20+T cell helper (Th) population is dominated by the Th1-subset (42.7 ± 15.0% and 42.9 ± 11.6%; respectively). In contrast, in CD20–T cells, the Th17 population was most often found (34,6± 19,3% and 38.0 ± 14.0%; respectively). CD20+T cell of SSc-R produced more IFNγ, TNFα and IL-2 compared to HC. During RTX therapy these cells were less capable to produce the cytokines.
In SSc-R a higher frequency of CD20+T cells, were already in the early apoptotic phase compared to HC (32,17 ± 13,66% vs. 7,5 ± 13,49%) and after heat exposure significantly more of these cells were found in the late apoptotic phase (LAP). Thus, in SSc patients 28,00 ± 24,88% were found in the LAP compared to 5,29 ± 4,30% in HC. This effect on apoptose seemed to be restricted to CD20+T cells, since it was not found in B cells of HC or SSc.
Conclusion: SSc patients have a lower percentage of CD20+T cells compared to HC and to the reported frequency in RA or MS. Whether patients with SSc have per se a lower number of this cell subset in general or these cells might localize into tissue has to be determined. Furthermore, the cytotoxic T cell population of SSc is enriched in CD20+ cells that produce a higher number of pro-inflammatory cytokines. The role of IFNγ -production by these cells in the fibrotic process in SSc is still unclear since there are reports, that indicate pro- as well as anti-fibrotic effects of this cytokine. Similar to previous reports the CD20+T cell population is prone to apoptosis. Whether the therapeutic effect of RTX is related to the preferential elimination of CD20+CD8+ T cells needs further investigation.
To cite this abstract in AMA style:D'Orazio M, Fliesser E, Moazedi-Fürst F, Stradner M, Kielhauser S, Fessler J, Brezinschek HP. Characterization of CD20+ T Cells in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/characterization-of-cd20-t-cells-in-patients-with-systemic-sclerosis/. Accessed August 3, 2020.
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