Background The pathogenesis of systemic sclerosis (SSc) is largely unknown, although proinflammatory cytokines are considered to play a central role. We hypothesized that Th17 and/or Tc17 cell populations and cytokine expression may be altered in SSc.
Objectives Our purpose was to investigate the pattern of expression of proinflammatory cytokines by peripheral blood (PB) IL-17+ T cell populations in SSc and to explore clinical associations.
Methods This study included 41 SSc patients and 20 age- and sex-matched healthy controls (HC). All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc and were classified according to LeRoy et al. as having limited cutaneous SSc (lSSc, n=29) or diffuse cutaneous SSc (dSSc, n=12). A clinical evaluation was made, including disease duration, disease activity as measured by the European Scleroderma Study Group criteria, modified Rodnan skin score (mRSS), digital necrosis and target organs’ involvement. The autoantibody profile was collected from medical records.
Each participant was submitted to a blood sample collection, which was processed in order to separately analyze the intracellular expression of IL-2, TNF-α and IFN-γ in IL-17+ T cell populations, within the CD4 and CD8 T cell subsets.
Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney test was used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant.
Results The mean age was 56.1±11.8 and 52.0±9.9 years for SSc patients and HC respectively. Females represented 78% of the SSc group and 80% of the HC. The patients had a mean mRSS of 11.32±7.76 and mean disease activity of 2.76±2.44.
The frequency of PB Th17 and Tc17 cells was not statistically different in SSc patients when compared to HC. The percentage of Th17 and Tc17 cells expressing IL-2 was significantly higher in SSc patients than in HC (p<0.001 and p=0.006, respectively). There were no differences in the frequency of Th17 and Tc17 cells expressing either TNF-α or IFN-γ between patients and controls.
There were no differences between lSSc and dSSc patients regarding the frequency of IL-2, TNF-α and IFN-γ expression among Th17 or Tc17 cells populations. We had similar negative findings regarding disease duration and internal organs’ involvement.
The frequency of IL-2-producing Th17 cells showed a positive correlation with mRSS (p=0.002). Conversely, the frequency of IL-2-producting Tc17 cells presented a positive correlation with disease activity (p=0.021). SSc patients with history of digital ulcer presented higher frequencies of IL-2 expression among Tc17 cells (p=0.001).
Conclusions IL-2-producing Th17 and Tc17 cells frequency is higher in SSc than in HC, no differences being found between the two clinical subtypes of the disease. The frequency of IL-2-producing Tc17 cells was correlated with disease activity whereas the frequency of IL-2-producing Th17 cells was correlated with the extension of skin involvement. These findings support the hypothesis that IL-2 produced by Th17 and Tc17 cells may be involved in the pathological process of SSc, regardless of the disease subset.
References Arthritis Rheum. 1992 Jan;35(1):67-72.
Disclosure of Interest None Declared