Abstract Introduction Autoimmune pulmonary alveolar proteinosis (APAP) generally has a favorable prognosis, with an 11-year survival rate of 86% from diagnosis. However, it is known that approximately 20% of APAP cases develop pulmonary fibrosis (PF). PF is a poor prognostic factor in APAP, and some cases progress to requiring lung transplantation. Nevertheless, the mechanisms underlying PF in APAP remain poorly understood. Peripheral blood mononuclear cells (PBMCs), as key immune cell populations, may be involved in the pathogenesis of respiratory diseases. Transcriptome analyses have revealed characteristic gene expression patterns in various respiratory disease pathologies. While APAP is primarily caused by dysfunction of alveolar macrophages, PBMC function may influence disease modification; however, the details remain unclear. Aims This study aims to investigate the pathogenesis of APAP and the mechanisms underlying its associated PF from the perspective of PBMC function. Methods RNA sequencing was performed on PBMCs from APAP patients. Differentially expressed genes (DEGs) were identified, and enrichment analyses were conducted for healthy controls (n = 5) vs APAP patients (n = 14), and for APAP patients with PF (n = 5) and those without PF (n = 9). Results Compared to healthy controls, APAP patients showed downregulation of NF-κB signaling pathways and viral infection defense pathways. Furthermore, compared to APAP patients without PF, those with PF showed greater suppression of actin depolymerization and reduced telomere maintenance. PIK3CA was identified as the DEG associated with the former pathway, RTEL1 and DNA2 were associated with the latter. Conclusion APAP with PF may share pathogenic mechanisms with idiopathic pulmonary fibrosis. PBMC transcriptomic profiles reflected disease-related immune alterations, suggesting that functional changes in PBMCs are involved in the pathogenesis of APAP and its PF progression. This abstract is funded by: None
Hirama et al. (Fri,) studied this question.