PMID- 37069968 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230419 IS - 2468-0249 (Electronic) IS - 2468-0249 (Linking) VI - 8 IP - 4 DP - 2023 Apr TI - Urinary T Cells Identify Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Predict Prognosis: A Proof of Concept Study. PG - 871-883 LID - 10.1016/j.ekir.2023.01.013 [doi] AB - 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 (T(reg)) 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 helper cells (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. CI - (c) 2023 International Society of Nephrology. Published by Elsevier Inc. FAU - Sonnemann, Janis AU - Sonnemann J AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental and Clinical Research Center, Charite-Universitatsmedizin Berlin and Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. AD - Berlin Institute of Health, Berlin, Germany. FAU - Klocke, Jan AU - Klocke J AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Bieringer, Markus AU - Bieringer M AD - Department of Nephrology, Helios Klinikum Berlin-Buch, Berlin, Germany. FAU - Rousselle, Anthony AU - Rousselle A AD - Experimental and Clinical Research Center, Charite-Universitatsmedizin Berlin and Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. FAU - Eckardt, Kai-Uwe AU - Eckardt KU AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Elitok, Saban AU - Elitok S AD - Department of Nephrology and Endocrinology, Ernst von Bergmann Klinikum, Potsdam, Germany. FAU - Popovic, Suncica AU - Popovic S AD - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Bachmann, Sebastian AU - Bachmann S AD - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Kettritz, Ralph AU - Kettritz R AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental and Clinical Research Center, Charite-Universitatsmedizin Berlin and Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. FAU - Salama, Alan D AU - Salama AD AD - Center for Nephrology, University College London, Royal Free Hospital, London, UK. FAU - Enghard, Philipp AU - Enghard P AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Deutsches Rheumaforschungszentrum Berlin (DRFZ). FAU - Schreiber, Adrian AU - Schreiber A AD - Department of Nephrology and Medical Intensive Care, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental and Clinical Research Center, Charite-Universitatsmedizin Berlin and Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. LA - eng PT - Journal Article DEP - 20230118 PL - United States TA - Kidney Int Rep JT - Kidney international reports JID - 101684752 PMC - PMC10105048 OTO - NOTNLM OT - ANCA OT - TH OT - Treg OT - vasculitis EDAT- 2023/04/19 06:00 MHDA- 2023/04/19 06:01 PMCR- 2023/01/18 CRDT- 2023/04/18 01:45 PHST- 2022/08/15 00:00 [received] PHST- 2022/12/19 00:00 [revised] PHST- 2023/01/05 00:00 [accepted] PHST- 2023/04/19 06:01 [medline] PHST- 2023/04/18 01:45 [entrez] PHST- 2023/04/19 06:00 [pubmed] PHST- 2023/01/18 00:00 [pmc-release] AID - S2468-0249(23)00014-1 [pii] AID - 10.1016/j.ekir.2023.01.013 [doi] PST - epublish SO - Kidney Int Rep. 2023 Jan 18;8(4):871-883. doi: 10.1016/j.ekir.2023.01.013. eCollection 2023 Apr.