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Urinary T Cells Identify Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Predict Prognosis: A Proof of Concept Study

Sonnemann, Janis; Klocke, Jan; Bieringer, Markus; Rousselle, Anthony; Eckardt, Kai-Uwe; Elitok, Saban; Popovic, Suncica; ... Schreiber, Adrian; + view all (2023) Urinary T Cells Identify Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Predict Prognosis: A Proof of Concept Study. Kidney International Reports , 8 (4) pp. 871-883. 10.1016/j.ekir.2023.01.013. Green open access

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Abstract

INTRODUCTION: Necrotizing crescentic glomerulonephritis is a major contributor to morbidity and mortality in Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Because therapy relies on immunosuppressive agents with potentially severe adverse effects, a reliable noninvasive 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 patients with AAV and 8 controls to evaluate their biomarker characteristics. These were compared to soluble markers, monocyte chemoattractant protein-1 (MCP-1), soluble CD163 (sCD163), soluble CD25 (sCD25), and complement C5a (C5a), measured using multiplex analysis. Available kidney biopsies (n = 21) were classified according to Berden. RESULTS: Patients with active renal AAV (rAAV) showed significantly higher urinary cell counts than those in remission, or those with extrarenal 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 regulatory T cells (Treg) proportions and CD4+/CD8+ ratio in blood and urine suggested that urinary cells reflect tissue migration rather than mere micro-bleeding. Furthermore, urinary Treg and T helper cells (TH17) 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.

Type: Article
Title: Urinary T Cells Identify Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Predict Prognosis: A Proof of Concept Study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ekir.2023.01.013
Publisher version: https://doi.org/10.1016/j.ekir.2023.01.013
Language: English
Additional information: © 2023 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: ANCA, TH, Treg, vasculitis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10171368
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