CONCISE COMMUNICATION Serum level of circulating syndecan-1: A possible association with proliferative vasculopathy in systemic sclerosis Ching-Ying WU, 1,2,3 Yoshihide ASANO, 1 Takashi TANIGUCHI, 1 Shinichi SATO, 1 Hsin-Su YU 2,3 1 Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan, 2 Department of Dermatology, 3 College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ABSTRACT Syndecan-1 is a member of the transmembrane heparan sulfate proteoglycan family, whose membrane-bound and soluble forms are involved in wound healing, inflammation and vascular biology. Because these physiological events are implicated in the pathogenesis of systemic sclerosis (SSc), we investigated the clinical association of serum syndecan-1 levels in this disease. Serum syndecan-1 levels were significantly higher in SSc patients, both in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), than in healthy individuals, while comparable between dcSSc and lcSSc groups. In late stage dcSSc patients (disease duration of >6 years), but not non-late stage dcSSc patients (≤6 years), serum syndecan-1 levels were significantly higher than in normal controls. More importantly, SSc patients with elevated serum syndecan-1 levels had higher prevalence of telangiectasia, elevated right ventricular systolic pressure and decreased diffuse capacity of the lung for carbon monoxide than those with normal levels. Therefore, soluble syndecan-1 may be related to the development of proliferative vasculopathy in SSc patients. Key words: angiogenesis, pulmonary arterial hypertension, syndecan-1, systemic sclerosis, vasculopathy. INTRODUCTION Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by immune abnormalities, vasculopathy and tissue fibrosis with unknown etiology. 1 Evidence has sug- gested that aberrant vascular activation and remodeling is a key pathological feature leading to tissue fibrosis and vascul- opathy characteristic of SSc. 2 Syndecans are a family of transmembrane heparan sulfate proteoglycans composed of four closely related proteins (synd- ecan 1–4). Syndecans consist of the highly conserved trans- membrane and cytoplasmic domains and the variable ectodomains that can be shed from the cell surface by matrix metalloproteinases and exert paracrine and autocrine effects. Both of membrane-bound and soluble syndecans regulate a variety of cell functions and behaviors, including growth, adhe- sion and movement, via integrating microenvironmental signals surrounding cells. This is mainly mediated by their roles as a receptor for extracellular matrix proteins and a reservoir for growth factors through binding via heparan sulfate chains. 3 Dif- ferent syndecans have distinct distributions in vivo. In adult tis- sues, syndecan-1 is stably expressed in epithelial and plasma cells, but the detection of syndecan-1 on endothelial cells and other immune cells is seemingly difficult due to its dynamic regulation. Experimental data on animal models and human samples suggest that both membrane-bound and soluble forms of syndecan-1 play roles in wound healing, inflammation and vascular biology. 4–7 Reflecting its various roles, soluble syndecan-1 levels positively correlate with disease activity of systemic lupus erythematosus and Crohn’s disease. 8,9 Based on these backgrounds, to investigate the potential role of synd- ecan-1 in SSc we evaluated the clinical correlation of serum syndecan-1 levels in this disease. METHODS Patients Serum samples were obtained from 65 SSc patients (30 diffuse cutaneous SSc [dcSSc] and 35 limited cutaneous SSc [lcSSc]) 10 who fulfilled the new classification criteria 11 and 20 healthy individuals after getting informed consent and institu- tional approval (University of Tokyo Graduate School of Medi- cine). Patients who had been treated with corticosteroids or immunosuppressants were excluded. The patients’ information is shown in Figure 1. Measurement of serum syndecan-1 levels Specific enzyme-linked immunosorbent assay kits were used to measure serum syndecan-1 levels (Abcam, Cambridge, UK). Briefly, polystyrene 96-well plates coated with antihuman synd- ecan-1 antibody were incubated with twofold diluted serum and biotinylated antihuman syndecan-1 antibody at room Correspondence: Yoshihide Asano, M.D., Ph.D., Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: yasano-tky@umin.ac.jp Received 15 January 2015; accepted 8 May 2015. 63 © 2015 Japanese Dermatological Association doi: 10.1111/1346-8138.12986 Journal of Dermatology 2016; 43: 63–66