Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis

Nat Commun. 2023 Oct 11;14(1):5789. doi: 10.1038/s41467-023-41328-0.

Abstract

The immunological basis of the clinical heterogeneity in autoimmune vasculitis remains poorly understood. In this study, we conduct single-cell transcriptome analyses on peripheral blood mononuclear cells (PBMCs) from newly-onset patients with microscopic polyangiitis (MPA). Increased proportions of activated CD14+ monocytes and CD14+ monocytes expressing interferon signature genes (ISGs) are distinctive features of MPA. Patient-specific analysis further classifies MPA into two groups. The MPA-MONO group is characterized by a high proportion of activated CD14+ monocytes, which persist before and after immunosuppressive therapy. These patients are clinically defined by increased monocyte ratio in the total PBMC count and have a high relapse rate. The MPA-IFN group is characterized by a high proportion of ISG+ CD14+ monocytes. These patients are clinically defined by high serum interferon-alpha concentrations and show good response to immunosuppressive therapy. Our findings identify the immunological phenotypes of MPA and provide clinical insights for personalized treatment and accurate prognostic prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Leukocytes, Mononuclear
  • Microscopic Polyangiitis* / drug therapy
  • Microscopic Polyangiitis* / genetics
  • Monocytes
  • Multiomics
  • Phenotype

Substances

  • Immunosuppressive Agents