Impaired alveolar regeneration in patients with Anti-MDA5+ DM associated rapidly progressive ILD

<bold>Introduction:</bold> Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (Anti-MDA5+ DM) is an autoimmune disease associated with rapidly progressive interstitial lung disease (RP-ILD) and a high mortality rate. The pathogenesis and poor prognosis of Anti-MDA5+ DM associated RP-ILD remain unclear. <bold>Objective:</bold> This study aimed to investigate the role of alveolar regeneration in Anti-MDA5+ DM associated RP-ILD. <bold>Methods:</bold> Samples were collected by transbronchial lung biopsy from 5 Anti-MDA5+DM patients and 5 donors from lung transplantation. Single cell RNA sequencing was obtained from the Human Cell Atlas Data Coordination Platform/NCBI BIOPROJECT. Histological analysis and the characterization of alveolar epithelial cells by immunofluorescent staining were performed. Single cell data processing was analyzed through R packages. <bold>Result:</bold> H&E and Masson staining revealed severe lung fibrosis in the Anti-MDA5+DM samples. The ratio of ki67+AT2 cells was significantly higher. Then we compared the differentiation of AT2 cells in Anti-MDA5+DM patients and donors. We found that the proportion of intermediate AT2 cells was significantly increased. Also, these results were consistent with single cell RNA-seq analysis. A majority of AT2 cells in Anti-MDA5+DM patients highly express KRT8. <bold>Conclusion:</bold> These findings indicate that alveolar lung regeneration was impeded in patients with Anti-MDA5+ DM associated RP-ILD <fig><object-id>erj;64/suppl_68/PA5299/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>