Figure 1: Three independent cohorts of chronic fibrosing IIPs were involved in this study.

(A) Cohort 1 consisted of 10 IPF and 10 INSIP patients, who satisfied multi-disciplinary diagnosis (MDD). Surgical lung biopsy was performed on all patients. The average follow-up periods after diagnosis of IPF and INSIP were 55 (range, 31–81) and 121 (range, 59–135) months, respectively. During the follow-up period, two INSIP patients were highly suspected to have collagen vascular diseases (CVDs) and excluded from the study. The remaining 18 patients from cohort 1, 10 patients with sarcoidosis (SAR), 10 patients with autoimmune pulmonary alveolar proteinosis (aPAP), and 10 healthy controls (HCs) were included in the protein array study (white box). (B) Cohort 2 consisted of 114 patients with chronic fibrosing IIPs (IPF, n = 19; non-IPF, n = 95), who consecutively visited the Osaka University Hospital between February 2014 and October 2014. Serum anti-MX1 autoantibody was measured in all patients in cohort 2 and 30 healthy controls, and the cut-off value for anti-MX1 autoantibody was determined (white box, left). Using this cut-off value, cohort 2 was divided into anti-MX1 autoantibody–positive (n = 20) and –negative (n = 94) groups, and a cross-sectional study was performed (white box, right). (C) Cohort 3 consisted of 155 patients with chronic fibrosing IIPs registered at National Hospital Organization Kinki-Chuo Chest Medical Center between 2005 and 2009. Among 84 non-IPF patients in cohort 3, five patients positive for serum anti-ARS antibody were removed. The remaining 79 patients were divided into anti-MX1 autoantibody–positive and –negative groups, and a nested case–control study was performed (white box).