Characterizing the lavage and serum cytokine profiles of interstitial pneumonia with autoimmune features and their implications for progressive fibrosis

Abstract Objective To explore whether cytokines could be potential biomarkers to predict the occurrence of the progressive fibrosis (PF) phenotype among patients with interstitial pneumonia with autoimmune features (IPAF). Methods This study prospectively collected 51 IPAF and 15 idiopathic pulmonary fibrosis (IPF) patients who were diagnosed at the First Affiliated Hospital of Guangzhou Medical University from July 2020 to June 2021. All IPAF patients were followed up for 1 year to assess the development of PF phenotype. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected at enrolment and analysed for differences in 39 cytokines expression. Principal component analysis (PCA) and cluster analysis were conducted to identify a subgroup of IPAF patients at high risk for developing the PF phenotype. Finally, cytokine differences were compared between subgroups to identify potential biomarkers for PF-IPAF occurrence. Results According to the PCA analysis, 81.25% of PF-IPAF patients share overlapped BALF cytokine profiles with IPF. Cluster analysis indicated that IPAF patients in subtype 2 had a higher risk of developing the PF phenotype within 1 year (P = 0.048), characterized by higher levels of CCL2 and CXCL12, and lower lymphocyte proportion (LYM%) in BALF. Elevated levels of BALF CCL2 (>299.16 pg/ml) or CXCL12 (>660.115 pg/ml) were associated with a significantly higher risk of developing PF phenotype within the 1-year follow-up period (P = 0.009, 0.001, respectively). Conclusion PF-IPAF phenotype exhibits similar inflammatory cytokine profiles to IPF. Cytokine CCL2 and CXCL12, and LYM% in BALF serve as potential biomarkers for predicting the PF phenotype in IPAF patients. Clinical Trial Registration Register: Qian Han, Website: http://www.chictr.org.cn/showproj.aspx?proj=61619, Registration number: ChiCTR2000040998.