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Abstract: SA-PO0743

Identification of Common Immune-Related Biomarkers and Potential Therapeutic Targets for Renal and Pulmonary Manifestations of ANCA-Associated Vasculitis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Meng, Yao, Zhongshan Hospital Fudan University, Shanghai, China
  • Liu, Tong, Zhongshan Hospital Fudan University, Shanghai, China
  • Li, Yana, Zhongshan Hospital Fudan University, Shanghai, China
  • Zhang, Weidong, Zhongshan Hospital Fudan University, Shanghai, China
  • Lu, Yufei, Zhongshan Hospital Fudan University, Shanghai, China
Background

ANCA-associated vasculitis (AAV) is a rapidly progressive autoimmune disorder that mainly affects kidney and lung, the precise mechanisms remain elusive.

Methods

Datasets of AAGN and IPF from GEO and immune-related genes from ImmPort were used. DEGs were identified by Limma package, co-expression modules by WGCNA. ROC evaluated hub gene diagnostic efficacy. CIBERSORT assessed immune cell infiltration, single-cell analysis got marker locations. Enrichr and molecular docking identified potential drugs.

Results

85 overlapping DEGs were identified in AAGN and IPF datasets. 128 common genes potentially driving their pathogenesis were discovered by WGCNA. Integrating DEGs and WGCNA module genes gave 207 candidate driver genes. Intersecting with immune-related genes yielded 22 hub genes (Figure A). TOP 10 genes in PPI network as candidate diagnostic markers, with IGF1 and CXCL12 being most significant (Figure B). In the AAGN and IPF training sets, IGF1 had an AUC > 0.7 and was replicated in the independent validation cohort (Figure C). CIBERSORT analysis showed that differently infiltrated immune cells in AAGN and IPF were regulated by shared hub genes (Figure D). 25 cell clusters were classified in 12 IPF samples, and localization analyses were done (Figure E). CXCL12 and IGF1 have the highest binding affinity for mifepristone and progesterone, respectively, indicating the key targets of AAV (Figure F).

Conclusion

This study shows the AAV kidney and lung lesions share immune-related biomarkers and pathogenic pathways. In addition, these two disease phenotypes reveal different immune cell infiltration microenvironments but are modulated by common genes.

Common Immune Biomarkers and Key Targets in AAV Bridging Renal and Pulmonary Pathologies

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)