Abstract
Objective: To find the biomarker of SSc at peptide level and to investigate the biological function of the molecule.
Methods: Sera form 40 patients with SSc, 30 SLE, 21 RA, 30 OA, and 26 healthy donors were used in peptidomic analysis. The biofunctions of complement DRC3f and C3f was testified by stimulating the cultured skin fibroblasts, skin and lung microvascular endothelial cells (MEC) with both recombinant peptides and the 3000 Dalton-filtered DRC3f-positive sera. The cell proliferation was observed on bioreduction of MTS into formazan by living cells. The production of TGF-beta, VEGF and EGF were measured by ELISA.
Results: A group of peptides with m/z of 1865, 1778, 1691, 1563, and 1450 were detected dominantly in SSc sera. These peptides were identified to be DRC3f and its derivatives. The levels of DRC3f was related to the age of the onset, frequency of interstitial pulmonary fibrosis, sicca complaints, and the severity of vascular impairment, as well as to the levels of Complement C3, C4, CH50, IgG, IgA, CRP, ESR and ANA. Synthesized DRC3f and C3f enhanced the MEC proliferation independent on growth factors. Furthermore, both the whole and filtered sera containing DRC3f enhanced proliferation of endothelial cells. DRC3f and C3f increased the production of TGF-beta by skin fibroblasts and MEC but not by lung MEC.
Conclusions: DRC3f, predominantly detected in SSc and related to disease severity and activity and functioning as growth factors, is a useful marker of SSc and may play important roles in pathogenesis of SSc.
