The genomic landscape of ANCA-associated vasculitis: Distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus

• DOI: 10.3389/fimmu.2023.1072598
• Publication Date: 2023-03-27T05:23:17Z
• Authors: Aggelos Banos; Konstantinos Thomas; Panagiotis Garant...; Anastasia Filia; Nikolaos Malissovas; Antigone Pieta; Dimitrios Nikolakis; Alexandros G. Pan...; Aglaia Chalkia; Dimitrios Petras; George Bertsias; Dimitrios T. Boumpas; Dimitrios Vassilo...
• Keywords: Microscopic polyangiitis; Systemic vasculitis

Introduction Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) present with a complex phenotype and are associated high mortality multi-organ involvement. We sought to define the transcriptional landscape molecular endotypes of AAVs compare it systemic lupus erythematosus (SLE). Methods performed whole blood mRNA sequencing from 30 patients AAV (granulomatosis polyangiitis/GPA microscopic polyangiitis/MPA) combined functional enrichment network analysis for aberrant pathways. Key genes pathways were validated in an independent cohort 18 patients. Co-expression hierarchical clustering analysis, identified endotypes. Multi-level overlap SLE was based on our published data 142 Results report here that “Pan-vasculitis” signature contained 1,982 differentially expressed genes, enriched leukocyte differentiation, cytokine signaling, type I II IFN signaling B-T cell immunity. Active disease characterized by signatures linked cycle checkpoints metabolism pathways, whereas ANCA-positive exhibited humoral immunity fingerprint. Differential expression GPA MPA yielded IFN-g pathway (in addition IFN) former related autophagy splicing latter. Unsupervised taxonomy revealed four neutrophil degranulation, B-cell responses as potential mechanistic drivers. Transcriptional perturbations heterogeneity more pronounced SLE. Molecular data-driven uncovered distinct could be exploited targeted therapy. Discussion conclude transcriptomic reveals The transcriptome is homogenous less fragmented compared which may account its superior rates response