FRI0245 SCCA-IGM Is Up-Regulated in Scleroderma Patients with Reduced DLCO: A New Biomarker of Pulmonary Involvement?. (15th July 2016) - Zanatta, E.
Abstract : Background: Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse fibrosis of skin and internal organs. The pulmonary involvement represents the first cause of death in these patients (1). The reduction of DLCO is the first functional alteration observed in interstitial lung disease (ILD). The detection of sera biomarkers predictive of ILD is still discussed in SSc. Squamous Cell Carcinoma Antigen (SCCA) is a serin protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, and in pulmonary tissue of patients with idiopathic ILD (2). SCCA is detectable in serum as free protein and as circulating immune complex coupled to IgM. Objectives: The aim of this study was to evaluate the serum levels of free SCCA and SCCA-IgM in a group of scleroderma patients and to investigate the correlation with different SSc subsets. Methods: Forty patients, 31 women and 9 men affected by SSc (according to ACR/EULAR 2013 criteria), with mean age of 55±2 years and mean disease duration of 14±8 years were recruited. Seventeen patients had the diffuse cutaneous form of SSc and 23 the limited one. ANA were positive in all subjects with specificity for ACA in 16 cases, anti-Scl70 in 14, anti-RNA polymerasis III in 3, without specific pattern in 7. We considered the avascular score (detected at nailfold capillaroscopy), the Rodnan skin score, the pulmonary function tests, the coronary flow reserve (CFR), EUSTAR score and the systolic pressure in pulmonary artery (PAPs) as clinical parameters. SCCA-IgM (AU/ml) and free SCCA (ng/ml) serum levels were measured in all patients using a validated ELISA assay. SCCA-IgM positivity was considered for values >200 AU/ml, according to our laboratory. Results: SCCA-IgM serum levels were found increased in 14 SSc patients (35%). We didn't find significant differences in patients with diffuse and limited cutaneous form of disease, and not even statistically significant correlations with skin score, avascular score, CFR and PAPS. SCCA-IgM and free SCCA levels were found significantly increased in patients with reduced DLCO (<75%) at pulmonary functions test in comparison to those without (p<0.05). At multivariate analysis SCCA-IgM positivity (OR: 6.25; CI: 1.26–31.02) and EUSTAR score >3 (OR: 7.75; CI: 1.28–46.3) were independently associated with diagnosis of ILD. Conclusions: Serum levels of SCCA-IgM and free SCCA were increased in a group of patients with SSc. Patients with reduced DLCO, the first functional alteration observed in ILD, showed a significant increase of SCCA-IgM. Futhermore this biomarker is independently associated with the diagnosis of ILD, suggesting a possible role of this molecule in the first phases of the pathogenesis of pulmonary involvement in systemic sclerosis. References: Steen VD, Medsger TA. Ann Rheum Dis 2007;66:940–4 Calabrese F et al. Thorax 2008;63:795–802. Disclosure of Interest: None declared