Anti-UBE2T antibody: a novel biomarker of progressive-fibrosing interstitial lung disease

Background Antifibrotic therapy has demonstrated efficacy against progressive-fibrosing interstitial lung disease (PF-ILD); therefore, it has become a priority to identify disease behavior before disease presentation. As autoimmunity is implicated in the pathogenesis of various ILDs, we explored the possibility of a circulating biomarker that can predict the chronic progressive behavior of ILDs. Methods A single-center retrospective cohort study was conducted to investigate a biomarker of PF-ILD. Circulating autoantibodies against 9,483 purified full-length human recombinant proteins of patients with interstitial pneumonia were screened by microarray analysis. The candidate auto-antibodies were verified their existence by multiples solution assay. In addition, enzyme-linked immunosorbent assay (ELISA) was performed in larger sample sets to evaluate accurate sensitivity, specificity and clinical significance in ILDs. Results In total, 61 healthy subjects and 87 patients with various ILDs enrolled in this study. Anti-UBE2T antibody was discovered by performing protein microarray and multiplex solution assay as a candidate biomarker of ILDs. By measuring its concentration by ELISA, anti-ubiquitin-conjugating enzyme E2T (UBE2T) antibody levels were significantly higher in patients with idiopathic interstitial pneumonias (IIPs), especially in those with PF-ILDs, than in healthy participants. The receiver operating characteristic analysis of anti-UBE2T antibody in diagnosing PF-ILD was calculated. The area under the curve was 0.85 and yielded a cut-off value of 238.1 ng/mL. Anti-UBE2T antibody-positive IIP patients demonstrated significantly higher ILD-gender age physiology scores, PF-ILD diagnosis rates and were more likely to develop honeycomb structures than anti-UBE2T-negative IIP patients after two years of follow up. The anti-UBE2T antibody positivity did not correlate with other commercial biomarkers such as KL-6 and commercial autoantibodies, suggesting the presence of anti-UBE2T antibody was independent of the others. Immunohistochemical staining of UBE2T in normal lungs was observed sparsely in the bronchiole epithelium and macrophages. Controversially, idiopathic pulmonary fibrosis lung tissue showed robust expression of the UBE2T protein in the lining epithelium of honeycomb structures. Conclusion This is the first report to describe anti-UBE2T antibody, a new biomarker that is significantly elevated in idiopathic PF-ILDs. This new antibody may constitute a sensitive biomarker to detect cases of PF-ILDs that are not currently detected by commercially available biomarkers.