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B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis

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Recent data suggests that rituximab may favorably affect skin fibrosis and lung function in patients with systemic sclerosis. Based on experimental data suggesting a key role of B and T cells in scleroderma we aimed to explore the effect(s) of rituximab treatment on T cell subpopulations. Fifteen patients with scleroderma who received rituximab treatment and six who received standard treatment alone were recruited. Peripheral CD4+IL4+, CD4+INFγ+, CD4+IL17+ and CD4+CD40L+ T cells were assessed using flow cytometry. Using ELISA, serum levels of IL4 were assessed. Skin CD4+IL4+ T cells were assessed with confocal microscopy from skin biopsies. Following rituximab treatment skin CD4+IL4+ T cells obviously decreased as seen with confocal microscopy. Moreover, peripheral CD4+IL4+ T cells decreased significantly compared to those from patients who received standard treatment alone: median (IQR): 14.9 (22.63–12.88) vs 7.87 (12.81–4.9)%, p = 0.005 and 9.43 (19.53–7.50)% vs 14.86 (21.96–6.75)%, p = NS at baseline and 6 months later respectively, whereas there was no difference in serum IL4 levels. Peripheral CD4+CD40L+ T cells also decreased significantly following rituximab treatment compared to those from patients who received standard treatment alone: median (IQR): 17.78 (25.64–14.44)% vs 8.15 (22.85–3.08)%, p = 0.04 and 22.13 (58.77–8.20)% vs 72.11 (73.05–20.45)%, p = NS at baseline and 6 months later respectively. Furthermore, peripheral CD4+INFγ+ and CD4+IL17+ T cells revealed no differences following rituximab treatment. Our study demonstrates a link between rituximab treatment and CD4+IL4+ T cell decrease both in the skin and peripheral blood of patients with SSc.

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This work was supported by the University of Patras through the “Karatheodori” unrestricted research Grant (D184) to Dimitrios Daoussis.

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Correspondence to Stamatis-Nick C. Liossis.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the “Patras University Hospital (Greece)” ethics committee (ISRCTN99672071) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Antonopoulos, I., Daoussis, D., Lalioti, ME. et al. B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis. Rheumatol Int 39, 1889–1898 (2019).

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