AB0146 Increased frequency of th1 and tc1 lymphocytes producing tumor necrosis factor alpha in peripheral blood of late-stage systemic sclerosis
Authors: M. G. Santiago, M. Raposo, C. Duarte, M. J. Salvador, A. Paiva, J. A. P. da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Substantial evidence supports the implication of immune-activated cells, cytokines and chemokines in the pathogenesis of systemic sclerosis (SSc). The frequency of T cells expressing activation markers is increased in the peripheral blood (PB) of SSc patients. Proinflammatory cytokines, such as IL-2, TNF-α and IFN-γ, seem to be mostly involved in immune responses at early stages of the disease. However, discrepancies exist between the results of several studies. <h3>Objectives</h3> We undertook the present study to investigate the pattern of expression of proinflammatory cytokines by PB Th1 and Tc1 populations and to explore associations with disease duration. <h3>Methods</h3> Forty SSc patients and 18 healthy controls (HC) were included. All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc (limited cutaneous SSc (lSSc, n=29) or diffuse cutaneous SSc (dSSc, n=11), according to LeRoy et al.). A further subdivision was made, based upon the duration of disease, as early- (n=11) and late-stage (n=30), and these groups were individually compared with HC. A thorough clinical evaluation was performed and registered. The autoantibody profile was collected from medical records. All patients signed an informed consent and provided a PB sample, which was processed to separately analyze the intracellular expression of IL-2, TNF-α and IFN-γ in Th1 and Tc1 cell populations. Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney and Kruskal-Wallis tests were used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman's correlation coefficient. P values &lt; 0.05 were considered statistically significant. <h3>Results</h3> The mean age was 56.0±11.9 and 51.7±9.9 years for SSc patients and HC respectively. Females represented 77.5% of SSc and 83.3% of the control group. The mean disease duration was 9.6±8.55 years, the mean mRSS was 11.60±7.65 and the mean disease activity was 2.74±2.47. The frequency of Th1 and Tc1 circulating cells was not statistically different between SSc patients and HC. The percentage of Th1 and Tc1 cells producing TNF-α was significantly higher in late-stage than in early-stage SSc (p=0.034 and p=0.005, respectively). The percentage of Tc1 cells producing IFN-γ was significantly lower in early-stage than in late-stage SSc (p=0.017). No statistically significant differences were observed between early and late-stage SSc, concerning IL-2 expression among Th1 and Tc1 cells and IFN-γ expression among Th1 cells. There were no significant association between disease subset, history of digital necrosis and internal organs' involvement, mRSS or disease activity and the frequency of IL-2, TNF-α and IFN-γ expression among Th1 or Tc1 cells. <h3>Conclusions</h3> The frequency of TNF-α-producing Tc1 cells was higher in late-stage SSc. The potential pathogenic relevance of these observations justifies further investigation, concerning the profile of proinflammatory cytokines and their potential involvement in different stages of the disease. <h3>References</h3> Arthritis Rheum. 1992 Jan;35(1):67-72. <h3>Disclosure of Interest</h3> None Declared