Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis

• Published in: International journal of rheumatic diseases Vol. 24; no. 5; pp. 711 - 718
• Main Authors: Ikawa, Tetsuya, Miyagawa, Takuya, Fukui, Yuki, Minatsuki, Shun, Maki, Hisataka, Inaba, Toshiro, Hatano, Masaru, Toyama, Satoshi, Omatsu, Jun, Awaji, Kentaro, Norimatsu, Yuta, Watanabe, Yusuke, Yoshizaki, Ayumi, Sato, Shinichi, Asano, Yoshihide
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2021
• Subjects: Angiogenesis; anti‐mitochondrial M2 antibody; Asymptomatic; Autoimmune diseases; Carbon monoxide; CCL20; CCL20 protein; Chemokines; Cholangitis; Fibrosis; Hypertension; Inflammation; Lung diseases; Mitochondria; primary biliary cholangitis; Pulmonary arteries; Pulmonary artery; pulmonary artery hypertension; Pulmonary hypertension; Scleroderma; Statistical analysis; Systemic sclerosis; Vascular diseases; anti-mitochondrial M2 antibody; systemic sclerosis; pulmonary artery hypertension; CCL20; primary biliary cholangitis
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.14103

Aim Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C‐C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. Method We conducted cross‐sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme‐linked immunosorbent assay. Statistical analyses were performed with the Mann‐Whitney U test, the Kruskal‐Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient. Results SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti‐mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. Conclusion Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.