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肾小管基底膜免疫复合物沉积与狼疮性肾炎的活动及进展相关:一项大型多中心中国研究。

Tubular basement membrane immune complex deposition is associated with activity and progression of lupus nephritis: a large multicenter Chinese study.

作者信息

Wang H, Xu J, Zhang X, Ren Y L, Cheng M, Guo Z L, Zhang J C, Cheng H, Xing G L, Wang S X, Yu F, Zhao M H

机构信息

1 Laboratory of Electron Microscopy, 26447 Peking University First Hospital , Beijing, PR China.

2 The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, PR China.

出版信息

Lupus. 2018 Apr;27(4):545-555. doi: 10.1177/0961203317732407. Epub 2017 Sep 27.

DOI:10.1177/0961203317732407
PMID:28954590
Abstract

Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort. A total of 102 lupus nephritis patients were enrolled from another four centers as the validation cohort. The status of TBM deposits was retrospectively assessed using electron microscopy, and the associations of the deposits with clinical data, pathological characteristics and renal outcomes were further analyzed. The percentage of positive TBM deposits was nearly 30% in the lupus nephritis patients. Using immuno-gold labeling, we found that 10/10 patients were positive for IgG, 7/10 were C3d positive, 6/10 were C1q positive, and 1/10 were C4d positive. Patients with TBM deposits presented with more active features, including a higher SLEDAI score (SLE Disease Activity Index) ( p < 0.001), higher serum creatinine level ( p = 0.001) and lower serum C3 level ( p < 0.001). These patients also presented with higher scores for most renal pathological indices, including the total activity indices score ( p < 0.001) and total chronicity indices score ( p = 0.001). TBM deposits affected renal outcomes in the univariate Cox hazards regression analysis (HR = 4.2, 95% CI = 1.3-14.3, p = 0.02). In conclusion, TBM deposits were common in lupus nephritis patients and correlated closely with the clinical disease activity and renal outcome.

摘要

肾小管间质损伤在狼疮性肾炎中很常见。免疫复合物沉积可发生于肾小管基底膜(TBM),但其在狼疮性肾炎患者中的意义尚不清楚。本研究在一个大型中国多中心队列中评估了有TBM沉积的狼疮性肾炎患者的临床和预后特征。从北京大学第一医院诊断为肾活检证实的狼疮性肾炎的195例患者中收集完整数据作为发现队列。另外从其他四个中心纳入102例狼疮性肾炎患者作为验证队列。采用电子显微镜回顾性评估TBM沉积状态,并进一步分析沉积与临床数据、病理特征和肾脏结局的相关性。狼疮性肾炎患者中TBM沉积阳性率近30%。采用免疫金标记法,我们发现10/10例患者IgG阳性,7/10例C3d阳性,6/10例C1q阳性,1/10例C4d阳性。有TBM沉积的患者表现出更活跃的特征,包括更高的SLEDAI评分(系统性红斑狼疮疾病活动指数)(p < 0.001)、更高的血清肌酐水平(p = 0.001)和更低的血清C3水平(p < 0.001)。这些患者大多数肾脏病理指标的评分也更高,包括总活动指数评分(p < 0.001)和总慢性指数评分(p = 0.001)。在单因素Cox风险回归分析中,TBM沉积影响肾脏结局(HR = 4.2,95%CI = 1.3 - 14.3,p = 0.02)。总之,TBM沉积在狼疮性肾炎患者中很常见,且与临床疾病活动和肾脏结局密切相关。

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