Sonnemann Janis, Klocke Jan, Bieringer Markus, Rousselle Anthony, Eckardt Kai-Uwe, Elitok Saban, Popovic Suncica, Bachmann Sebastian, Kettritz Ralph, Salama Alan D, Enghard Philipp, Schreiber Adrian
Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Kidney Int Rep. 2023 Jan 18;8(4):871-883. doi: 10.1016/j.ekir.2023.01.013. eCollection 2023 Apr.
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.
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 ( = 21) were classified according to Berden.
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) proportions and CD4/CD8 ratio in blood and urine suggested that urinary cells reflect tissue migration rather than mere micro-bleeding. Furthermore, urinary T and T helper cells (T17) patterns were associated with clinical response and risk of renal relapse.
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.
坏死性新月体性肾小球肾炎是抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）发病和死亡的主要原因。由于治疗依赖于具有潜在严重不良反应的免疫抑制剂，因此需要一种可靠的非侵入性疾病活动生物标志物来指导治疗。
我们使用流式细胞术对95例AAV患者和8例对照的血液和尿液样本中的T细胞亚群进行定量，以评估其生物标志物特征。将这些结果与使用多重分析测量的可溶性标志物单核细胞趋化蛋白-1（MCP-1）、可溶性CD163（sCD163）、可溶性CD25（sCD25）和补体C5a（C5a）进行比较。对可用的肾活检样本（n = 21）按照伯登分类法进行分类。
活动性肾AAV（rAAV）患者的尿细胞计数显著高于缓解期患者、肾外表现患者或健康对照。与MCP-1和sCD163相比，尿T细胞对疾病活动具有更强的区分能力，表现更优。根据伯登分类法肾活检被归类为“新月体性”的患者尿T细胞计数更高。血液和尿液中失调的调节性T细胞（Treg）比例以及CD4/CD8比值表明，尿细胞反映的是组织迁移而非单纯的微出血。此外，尿Treg和辅助性T细胞17（Th17）模式与临床反应和肾复发风险相关。
尿T细胞反映了AAV中的肾炎症环境，并为这种慢性疾病的发病机制提供了进一步的见解。它们作为非侵入性诊断和预后生物标志物的潜力值得进一步探索。
