The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers.

The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers.
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DOI:
10.1186/s13075-015-0600-y
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发表时间:
2015-04-03
影响因子:
4.9
通讯作者:
Riemekasten G
Riemekasten G
中科院分区:
医学2区
文献类型:
--
作者:
Kopetschke K;Klocke J;Grießbach AS;Humrich JY;Biesen R;Dragun D;Burmester GR;Enghard P;Riemekasten G

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尿T细胞是增殖性狼疮肾炎(LN)的可靠非侵入性生物标志物。尽管尿中T细胞亚群、B细胞和巨噬细胞可能进一步提高LN尿细胞生物标志物的有效性,但对它们的存在知之甚少。我们用流式细胞术分析了活动性LN患者(n = 19),其他系统性红斑狼疮(SLE)患者(n = 79)和糖尿病肾病(DN; n = 14)和抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV; n = 11)患者的同期血液和尿液样本。尿T细胞、B细胞和巨噬细胞的数量与疾病活动性相关,活动性LN组显著高于对照组。活动期LN患者尿T细胞、CD 8 + T细胞(AUC = 1.000)和CD 4 + T细胞(AUC = 0.9969)差异显著。CD 19 + B细胞(AUC = 0.7823)和CD 14+巨噬细胞(AUC = 0.9066)以及临床标准蛋白尿(AUC = 0.9201)未能达到这些高标准。DN或AAV患者也显示尿细胞计数增加,尽管SLE患者的CD 4/CD 8比值显著低于DN患者(p = 0.0006)。活动期LN患者尿中CD 4 + T细胞以效应记忆型为主,CD 40 L和Ki 67表达明显高于相应血细胞。尿Treg计数与疾病活动相关。尽管尿中可检测到B细胞和巨噬细胞计数,但T细胞仍然是LN的最佳尿细胞生物标志物。低的CD_4/CD_8比值似乎是LN的特征。本文的在线版本(doi:10.1186/s13075-015-0600-y)包含补充材料,可供授权用户使用。
Urinary T cells represent a reliable noninvasive biomarker for proliferative Lupus nephritis (LN). Little is known about the presence of T cell subsets, B cells and macrophages in the urine although they may further improve the validity of urinary cellular biomarkers for LN. We analyzed contemporaneous blood and urine samples of patients with active LN (n = 19), other Systemic Lupus Erythematosus (SLE) patients (n = 79) and urine samples of patients with diabetic nephropathy (DN; n = 14) and anti-neutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV; n = 11) by flow cytometry. Numbers of urinary T cells, B cells and macrophages correlated with disease activity and were significantly higher in the active LN group. Urinary T cells showed excellent distinction of patients with active LN, CD8+ T cells (AUC of ROC = 1.000) and CD4+ T cells (AUC = 0.9969) alike. CD19+ B cells (AUC = 0.7823) and CD14+ macrophages (AUC = 0.9066), as well as the clinical standard proteinuria (AUC = 0.9201), failed to reach these high standards. Patients with DN or AAV also showed increased urinary cell counts, although the CD4/CD8-ratio was significantly lower in SLE compared to in DN (p = 0.0006). Urinary CD4+ T cells of active LN patients proved to be mainly of effector memory phenotype and expressed significantly more CD40L and ki67 than corresponding blood cells. Urinary Treg counts correlated with disease activity. Despite of detectable urinary cell counts for B cells and macrophages, T cells remain the best urinary cellular biomarker for LN. A low CD4/CD8-ratio seems to be characteristic for LN. The online version of this article (doi:10.1186/s13075-015-0600-y) contains supplementary material, which is available to authorized users.
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