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Urinary T cells identify renal ANCA-associated vasculitis and predict prognosis: a proof of concept study

Authors

  • J. Sonnemann
  • J. Klocke
  • M. Bieringer
  • A. Rousselle
  • K.U. Eckardt
  • S. Elitok
  • S. Popovic
  • S. Bachmann
  • R. Kettritz
  • A.D. Salama
  • P. Enghard
  • A. Schreiber

Journal

  • Kidney International Reports

Citation

  • Kidney Int Rep 8 (4): 871-883

Abstract

  • OBJECTIVE: Necrotizing crescentic glomerulonephritis (NCGN) is a major contributor to morbidity and mortality in ANCA-associated vasculitis (AAV). Since therapy relies on immunosuppressive agents with potentially severe adverse effects, a reliable non-invasive biomarker of disease activity is needed to guide treatment. METHODS: We used flow cytometry to quantify T cell subsets in blood and urine samples from 95 AAV patients and 8 controls to evaluate their biomarker characteristics. These were compared to soluble markers (MCP-1, sCD163, sCD25, and C5a) measured using multiplex analysis. Available kidney biopsies (n = 21) were classified according to Berden. RESULTS: Patients with active renal AAV showed significantly higher urinary cell counts than those in remission or with extra-renal manifestation or healthy controls. Urinary T cells showed robust discrimination of disease activity with superior performance compared to MCP-1 and sCD163. Patients whose kidney biopsies had been classified as "crescentic" according to Berden classification showed higher urinary T cell counts. Discordant T(reg) cell proportions and CD4(+) / CD8(+) ratio in blood and urine suggested that urinary cells reflect tissue migration rather than mere micro-bleeding. Furthermore, urinary T(reg) and T(H)17 patterns were associated with clinical response and risk of renal relapse. CONCLUSION: Urinary T cells reflect the renal inflammatory milieu in AAV and provide further insights into the pathogenesis of this chronic condition. Their promising potential as noninvasive diagnostic and prognostic biomarkers deserves further exploitation.


DOI

doi:10.1016/j.ekir.2023.01.013