CXCR3+CD4+T Cells Are Enriched in Inflamed Kidneys and Urine and Provide a New Biomarker for Acute Nephritis Flares in Systemic Lupus Erythematosus Patients
CXCR3+CD4+T Cells Are Enriched in Inflamed Kidneys and Urine and Provide a New Biomarker for Acute Nephritis Flares in Systemic Lupus Erythematosus Patients
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DOI：
10.1002/art.24136
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发表时间：
2009-01-01
影响因子：
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通讯作者：
Riemekasten, G.
中科院分区：
文献类型：
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作者：
Enghard, P.;Humrich, J. Y.;Riemekasten, G.
Objective.狼疮性肾炎患者间质浸润中CD 4 + T细胞的高频率表明这些细胞对局部发病机制的贡献。本研究的目的是检查CXCR 3和趋化因子CXCL 10在招募这些细胞进入肾脏中的作用，并确定是否可以在尿液中监测浸润性T细胞，为急性狼疮性肾炎提供可靠的生物标志物。采用免疫组化和免疫荧光法检测了18例狼疮性肾炎患者肾组织中CD 3 + T细胞、CXCR 3+细胞和CXCL 10+细胞的分布。采用流式细胞术检测38例系统性红斑狼疮（SLE）患者外周血和尿液中CXCR 3 + CD 4 + T细胞的频率，并与SLE疾病活动指数（SLE疾病活动指数）进行比较。在狼疮性肾炎患者的肾活检组织中，平均63%的浸润细胞表达CXCR 3，类似于其中60%是T细胞，并且CXCR 3+细胞与CXCL 10-产生细胞共定位。在SLE急性肾炎患者的活检组织中，与外周血中的22%相比，尿液中接近50%的CD 4 + T细胞为CXCR 3+，并且尿液中CXCR 3 + CD 4 + T细胞的频率与疾病活动性相关。此外，尿中CD 4 + T细胞的数量反映了肾炎的活动性，每100 ml尿中CD 4 + T细胞高于800个可明显区分活动性和非活动性肾炎。CXCR 3 + T细胞被募集到发炎的肾脏中，在尿液中富集，并且是SLE中肾炎活动的有价值的标志物。它们也为未来的治疗提供了潜在的靶点。
Objective. The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored in the urine to provide a reliable biomarker for acute lupus nephritis.Methods. The frequencies of CD3+ T cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and immunofluorescence analyses of kidney sections from 18 patients with lupus nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry of peripheral blood and urine from 38 patients with systemic lupus erythematosus (SLE), and the values were compared with disease activity as determined by the Systemic Lupus Erythematosus Disease Activity Index.Results. In renal biopsy tissues from patients with lupus nephritis, a mean of 63% of the infiltrating cells expressed CXCR3, similar to 60% of them were T cells, and the CXCR3+ cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE patients with acute nephritis, similar to 50% of the urinary CD4+ T cells were CXCR3+, as compared with 22% in the peripheral blood, and the frequency of urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number of urinary CD4+ T cells reflected nephritis activity, and elevation above 800 CD4+ T cells per 100 ml of urine sharply delineated active from inactive nephritis.Conclusion. CXCR3+ T cells are recruited into the inflamed kidneys, are enriched in the urine, and are a valuable marker of nephritis activity in SLE. They also present a potential target for future therapies.