The Serum Levels Of Biomarkers (CXCL5,E-Selectin,VEGF,IL-33,IL-35)about Vascular Injury And Clinical Significance During The Course Of Systemic Sclerosis

Objective:A variety of adhesion molecules,chemokines and inflammatory factors were involved in microvascular injury of systemic sclerosis(SSc).The study aimed to determine vascular endothelial growth factor(VEGF),E-selectin,CXCL5,IL-33 and IL-35,analyze the correlation with clinical features,and explore the possible role played in SSc vasculopathy.Methods:According to SSc 1980 ACR criteria or 2013 ACR / EULAR classification criteria,52 SSc patients were included in the study.Serum levels of VEGF,E-selectin,CXCL5,IL-33 and IL-35 were measured by Multiple Immunoassays for Flow.30 age-matched and sex-matched healthy volunteers(HC)and 20 other connective tissue patients with Raynaud’s phenomenon(DC)were used as controls.Age,gender,disease duration,type of hardening of the skin,finger ulcers,organ involvement,ESR,CRP and NFC(only three patients refused the examination)of SSc patients were collected.VEGF,E-selectin,CXCL5,IL-33 and IL-35 serum levels and correlation with clinical parameters were analysed.Results:⑴ Serum concentrations of E-selectin in SSc patients and DC were higher than the HC group,whereas CXCL5 were lower(P<0.05).VEGF levels of SSc group were higher than DC(P<0.05).IL-35 levels was higher than HC.Between SSc patients,DC and HC,no differences could be detected for IL-33.⑵ For dcSSc patients VEGF and CXCL5 levels were significantly higher than sine and lcSSc group respectively(P<0.05).⑶ Patients with fingertip ulcers or cardiac involvement were found to have lower levels of CXCL5 than patients without fingertip ulcers or cardiac involvement(P<0.05).For renal involvement SSc patients,Serum levels of E-selectin and VEGF were higher than non-renal involvement group(P<0.05).⑷ VEGF and mRSS were closely positively related(P= 0.054).⑸ For SSc patients with fingertip ulcers,pulmonary fibrosis,cardiac involvement,gastrointestinal,renal and hematological involvement,”active” NFC accounted for higher proportion(P<0.05).mRSS and positive rate of anti-ACA antibody,anti-Scl-70 and anti-U1 RNP in “active pattern”were significantly higher than other groups(P<0.05).⑹ E-selectin serum levels in“active pattern” was higher than “early” and” late”pattern(P<0.05).⑺ E-selectin was negatively associated with of capillaries branches(P<0.05).VEGF was related to microbleeding negatively(P=0.056).Conclusions:E-selectin,CXCL5,IL-35,VEGF were involved in SSc vasculopathy.⑴Not only Eselectin was a predictor of renal involvement but also assocaited with the vasculopathy of“activity NFC” and capillaries branches.E-selectin could be a useful biomarker to monitor disease activity.⑵CXCL5 downregulation predicted finger ulcers and cardiac involvement.⑶VEGF involved in angiogenesis and skin fibrosis of SSc not only reflected renal involvement,but was related to NFC microbleeding.VEGF could be a diagnosis tool to distinguish from connective tissue disease patients with Raynaud’s phenomenon.⑷IL-35 involved in SSc vasculopathy may play a role in the regulation of immune suppression.