Background Systemic sclerosis (SSc) is a chronic inflammatory disease with complex pathogenesis. The role of regulatory T cells (Tregs) in the development of SSc has started being studied during the… Click to show full abstract
Background Systemic sclerosis (SSc) is a chronic inflammatory disease with complex pathogenesis. The role of regulatory T cells (Tregs) in the development of SSc has started being studied during the last decade with new aspects being disclosed continuously. Although there is a general agreement in the medical literature regarding the decreased functional capacity of circulating Tregs in SSc, the alteration of absolute number of Treg and Th17 cells as well as their associations with clinical characteristics of SSc are still unclear. Objectives The aim of the present study was to explore the relationship between absolute reduction of peripheral CD4 +regulatory T and Th17 cell subset and clinical characteristics in SSc patients. Methods The peripheral CD4 +T subsets from 54 patients with SSc and 30 healthy control subjects were analysed. The patients were divided into the untreated group (n=29) and treated group (n=25). The patients were also divided into group 1 (n=9) for the prominent pulmonary lesions, group 2 (n=5) for prominent esophageal involvement, group 3 (n=8) for both lung lesions and esophageal involvement, and group 4 (n=10) who had fingers swelling, sclerosis, ulceration prominent. Directly using the results from flow cytometry combined with internal standard beads, absolute number of peripheral Th17 and Treg cells from the subjects in each group were calculated.Abstract FRI0450 – Figure 1 Comparison of the levels of CD4+T lymphocyte subgroups among different groups. (A) The percentage of Th2 cells were significantly increased in untreated group compared with healthy controls. (B) The number of CD4*CD25*FOXP3*Treg cells decreased in patients with prominent pulmonary lesions. (C) The ratio of Th1/Th2 cells was not found to be significantly decreased in each group. *P < 0.05; **P < 0.01; *** P < 0.001.Abstract FRI0450 – Figure 2 Comparison of absolute number of Treg and Tb17 cells in each group with different clinical manifestations. (A) The number of Th17 cells were significantly increased in group 4 compared with group 1 and group 2. (B) The number of CD4+CD25+FOXP3+Treg cells decreased in patients with SSc. (C) The ratio of Th17/Treg cells was no statistically significant different in each group. *P < 0.1; **P < 0.01; *** P < 0.01. Results Although there were some changes among CD4 +T cell subsets in peripheral blood from these SSc patients, the major alteration was the reductions of Treg cell absolute number. Compared with the normal controls, the number of CD4+CD25+FOXP3+Treg cells were significantly decreased in untreated group (p=0.029) , in group 1 (p=0.014) and in group 2 (p=0.073) as compared with heathy controls. Interestingly, Tregs in group 2 were significantly lower than those in group 1 (p=0.006), in group 3(p=0.098) and in group 4(p=0.034). In addition, the number of Th17 cells were significantly higher in group 3 (p=0.003 and 4 (p<0.001 when compared with the normal controls, as well as in group 4 was significantly higher than that in group 1 (p=0.044), in group 2 (p=0.016), moreover, the number of Th17 cells in group 3 was significantly higher than that in group 2 (p=0.017). Conclusions The absolute number of peripheral CD4 +CD25+FOXP3+Treg cells decreased in untreated patients, indicating that this reduction arising from the disease itself. Our findings suggest that the severity of clinical manifestations in patients with SSc is related to the absolute decrease of peripheral Treg cells. Although there was no statistically significant different, absolute number of the Treg cells trended to decrease in patients who had more severe clinical manifestations. With the involvement of vital organs, the absolute number of Treg cells decreased more significantly. Moreover, in patients with relatively mild clinical manifestations, the increase in the absolute number of Th17 cells is even more obvious, suggesting that Th17 also plays an important role in early and intermediate stages. Disclosure of Interest None declared
               
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