B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis
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Rheumatology International https://doi.org/10.1007/s00296-019-04350-4
INTERNATIONAL
OBSERVATIONAL RESEARCH
B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis Ioannis Antonopoulos1 · Dimitrios Daoussis1 · Maria‑Eleni Lalioti2 · Theodora E. Markatseli3 · Alexandros A. Drosos3 · Stavros Taraviras2 · Andrew P. Andonopoulos1 · Stamatis‑Nick C. Liossis1 Received: 5 May 2019 / Accepted: 15 June 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract 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. Keywords Scleroderma · Rituximab · Lymphocytes · B cells · T cells
Introduction Systemic sclerosis (SSc) is a rheumatic disease with a complex pathogenesis comprising of autoimmune phenomena, vascular damage and fibrosis. Hence a considerable amount of research has focused on a better understanding of the pathogenic mechanisms that govern the disease process. Rituximab (RTX) is a chimeric monoclonal antibody * Stamatis‑Nick C. Liossis [email protected] 1
Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, 26504 Patras, Greece
2
Department of Physiology, School of Medicine, University of Patras, Rion, 26504 Patras, Greece
3
Department of Rheumatology, Ioannina University Hospital, University of Ioannina Medical School, Ioannina, Greece
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