Vasculitis & polymyalgia rheumatica

Single-cell multiomics reveals activation of the STAT3–PIM1 axis in T-cell subsets in proteinase 3-ANCA–positive granulomatosis with polyangiitis

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

These findings indicate that circulating CD4⁺ T cells in active PR3-GPA are characterised by activation of the STAT3-PIM1 axis, potentially driven by upstream IL-6 signalling.

Study context

Population
Patients with PR3-ANCA-positive granulomatosis with polyangiitis (GPA) (PR3-GPA), active disease and remission, and healthy controls; kidney biopsies from PR3-ANCA-associated crescentic glomerulonephritis
Comparison
Active PR3-GPA vs remission vs healthy controls
Outcome
Molecular signatures of CD4⁺ T cells associated with disease activity
Methodological detailssingle-cell multiomics (Single-cell RNA sequencing (scRNA-seq), Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq)), validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry, including phospho-flow cytometry, spatial transcriptomics of kidney biopsies
  • Single-cell multiomics (scRNA-seq, CITE-seq)
  • Validation by RT-qPCR and flow cytometry, including phospho-flow cytometry
  • Spatial transcriptomics of kidney biopsies

Main finding

As reported in the abstract

  • Upregulated PIM1 expression in CD4⁺ T-cell subsets in active GPA vs controls (scRNA-seq, CITE-seq)
  • Elevated PIM1, SOCS3 and STAT3 expression in CD4⁺ T cells in active disease (RT-qPCR, flow cytometry)
  • STAT3 phosphorylation and serum IL-6 increased in active GPA
  • Pim kinase inhibition reduced CD4⁺ T-cell activation, proliferation and cytokine production
  • Upregulated STAT3 and PIM kinase expression in inflamed regions of PR3-ANCA-associated glomerulonephritis biopsies (spatial transcriptomics)

Original publication

Single-cell multiomics reveals activation of the STAT3–PIM1 axis in T-cell subsets in proteinase 3-ANCA–positive granulomatosis with polyangiitis. Ann Rheum Dis. Published 28 May 2026. doi:10.1016/j.ard.2026.05.003

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