Background/Purpose: The TNF Superfamily member LIGHT (TNFSF14) regulates immune response and angiogenesis. Moreover, recent studies indicate that interactions of LIGHT with its receptor, TNFRSF14, might also play a role in regulation of tissue remodeling. Since autoimmunity, vascular injury and fibrosis are key elements of the pathogenesis of systemic sclerosis (SSc) we hypothesized that LIGHT might be involved in development of SSc. This study was aimed to assess potential role of LIGHT in SSc through evaluation of: 1). expression of LIGHT and its receptor, TNFRSF14, in skin biopsies and 2) associations between serum concentration of LIGHT and clinical features in SSc patients.

Methods: Expression of LIGHT and its receptor, TNFRSF14, was investigated by means of immunohistochemistry, and evaluated semiquantitatively (score from 0 to 3), in skin biopsies from 18 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using commercially available ELISA kits in 320 patients with SSc and 50 control subjects.

Results: Expression of both, LIGHT and TNFRSF14 was significantly higher in skin biopsies from SSc patients as compared with healthy controls (p<0.05). Patients with early SSc (</= 3 years from the first non-Raynaud’s phenomenon, n=13) showed significantly higher skin expression of TNFRSF14 (p<0.05) and tended to have greater skin expression of LIGHT (p=0.06) as compared with SSc patients with longer disease (n=5).

The mean serum concentration of LIGHT was significantly higher in SSc patients as compared with the controls (p<0.05). Moreover, mean serum concentration of LIGHT was significantly higher in SSc patients with digital ulcers (DUs) as compared with SSc patients without DUs, patients without anti-centromere antibodies (ACA) as compared with those with ACA, patients with muscle involvement (defined by elevated serum CK levels) compared with patients without CK elevation and in patients receiving steroids, as compared with those without steroid therapy (p<0,05 for all comparisons). In addition, the mean concentration of LIGHT was significantly higher in male patients as compared with female SSc patients (p<0,05). There were also statistically significant (p<0.05) although very weak correlations between serum concentration of LIGHT and skin involvement (modified Rodnan skin score (mRSS); R-Spearman = 0,13;), erythrocyte sedimentation rate (ESR; R-Spearman = 0,15), and, inverse, with diffusing capacity of the lungs for CO (DLCO; R-Spearman = -0,22). We could not find any significant associations between serum LIGHT concentrations and other SSc features, including subtype of SSc, disease duration, presence of interstitial lung disease, pulmonary hypertension, or other antibodies. In multivariate regression analysis including, as predictors, DUs, ACA, serum CK elevation, steroid therapy, mRSS, DLCO, ESR, and sex, only presence of DUs and DLCO were independently associated with serum concentration of LIGHT (p<0,05 for both) .

Conclusion: These data provide the first evidence of overexpression of LIGHT and its receptor in SSc and suggest that LIGHT-TNFRSF14 axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-expression-of-the-tnf-superfamily-member-lighttnfsf14-and-its-receptor-tnfrsf14-in-patients-with-systemic-sclerosis/