Squamous cell carcinoma antigen-IgM (SCCA-IgM) is associated with interstitial lung disease in systemic sclerosis

Objective: Interstitial lung disease (ILD) is the major determinant of prognosis in patients with systemic sclerosis (SSc). Squamous Cell Carcinoma Antigen (SCCA1) is a serin protease inhibitor which plays a pivotal role in inflammation and fibrosis. SCCA1 is overexpressed in pulmonary tissue of patients with idiopathic pulmonary fibrosis and can be detectable in serum as circulating immune complex bound to IgM (SCCA-IgM). We aimed to investigate the association between SCCA-IgM and clinical features of patients with SSc. Methods: Ninety-seven patients with SSc (ACR/EULAR criteria) were consecutively enrolled in the study. Clinical and serological variables and organ involvement were recorded. Pulmonary involvement was investigated by high-resolution CT (HRCT) and respiratory function tests. SCCA-IgM serum levels were measured by a validated ELISA assay (Hepa-IC, Xeptagen, Venice, Italy). We set the cut-off value for serum levels of SCCA-IgM > 200 AU/ml, calculated as mean + 3 standard deviations in 100 healthy subjects. Results: Forty-one (42.3%) patients were affected with ILD. SCCA-IgM values were significantly higher in patients with ILD than in those without: 218 (80-402) vs. 87.5 (59-150) AU/mL, P = 0.003. Patients with positive SCCA-IgM had more frequently ILD (69.7% vs. 28.1%, P ≤ 0.0001) and a lower total lung capacity (TLC) (P = 0.024) compared with negative ones. No differences were found in any other clinical and serological features. At multivariate analysis, SCCA-IgM was found to be associated with ILD diagnosis (OR 10.6, IC 2.9-38.4, P = 0.001). Conclusion: SCCA-IgM is associated with interstitial lung disease in scleroderma patients and might be used in the assessment of SSc-ILD.