Pang Yun, Tan Ying, Li Yongzhe, Zhang Jianchun, Guo Yongbing, Guo Zhiling, Zhang Chengying, Yu Feng, Zhao Ming-Hui
From the Renal Division, Department of Medicine, Peking University First Hospital, Beijing, P.R. China (YP, YT, FY, M-HZ); Institute of Nephrology, Peking University, Beijing, P.R. China (YP, YT, FY, M-HZ); Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, P.R. China (YP, YT, FY, M-HZ); Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China (YP, YT, FY, M-HZ); Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, P.R. China (YL); Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China (YL); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, P.R. China (YL); Renal Division, Jing Dong Yu Mei Traditional Chinese Medicine and Western Medicine Integrative Kidney Disease Hospital, Hebei, P.R. China (JZ); Department of Nephrology, Anyang District Hospital, Henan, P.R. China (YG); Department of Nephrology, First Affiliated Hospital of Henan University of Science and Technology, Henan, P.R. China (ZG); Department of Nephrology, Beijing General Hospital of Armed Police Forces, Beijing, P.R. China (CZ); Department of Nephrology, Peking University International Hospital, Beijing, P.R. China (FY); and Peking-Tsinghua Center for Life Sciences, Beijing, P.R. China ( M-HZ).
Medicine (Baltimore). 2016 Jan;95(3):e2520. doi: 10.1097/MD.0000000000002520.
Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.
狼疮性肾炎总是会引发肾脏的免疫炎症性组织损伤。五聚体3（PTX3）主要在炎症部位产生，已知其参与固有免疫系统的调节。本研究旨在调查来自一个大型中国队列的狼疮性肾炎患者的血清和尿液中PTX3水平，以及PTX3在肾组织中的表达。该研究采用横断面调查，纳入了288例活动性狼疮性肾炎患者，包括发现队列和验证队列，115例无临床肾脏受累的系统性红斑狼疮（SLE）患者以及46例健康对照。通过酶联免疫吸附测定（ELISA）筛查血清和尿液中的PTX3。通过免疫组织化学和免疫荧光检测PTX3的肾脏沉积。狼疮性肾炎发现队列中的血清PTX3平均水平显著高于无肾脏受累的SLE组和正常对照组（分别为P＜0.001，P＜0.001），验证队列也证实了这一点。15例缓解期的狼疮性肾炎患者的血清PTX3水平与活动期相比显著降低。血尿患者（P = 0.014）、白细胞尿患者（P = 0.002）、急性肾衰竭患者（P = 0.001）和肾病综合征患者（P = 0.036）的血清PTX3水平显著更高。在活动性狼疮性肾炎患者中，血清PTX3水平与系统性红斑狼疮疾病活动指数（SLEDAI）评分、血清肌酐值、肾脏病理活动指数以及血清补体3（C3）之间存在显著相关性。与缓解期患者和正常对照组相比，活动性狼疮性肾炎患者的尿液PTX3水平显著更高（分别为P = 0.011，P = 0.008）。尿液PTX3水平与肾小管间质病变的多个指标之间存在显著关联，包括尿液中的肾损伤分子-1（KIM-1）（r = 0.368，P = 0.016）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）（r = 0.320，P = 0.039）、微量白蛋白（r = 0.621，P = 0.003）、转铁蛋白（r = 0.451，P = 0.040）水平以及肾脏病理指标评分，尤其是活动性狼疮性肾炎患者的间质炎症（r = 0.349，P = 0.025）。血清和尿液PTX3水平之间存在显著相关性（r = 0.431，P = 0.006）。PTX3染色主要在狼疮性肾炎患者的肾小管间质区域观察到，免疫荧光研究表明PTX3可与间质中的成纤维细胞共定位。活动性狼疮性肾炎患者的循环和局部PTX3水平显著升高，可能是该疾病进展尤其是肾小管间质损伤的生物标志物。
