Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis
Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis
复制标题
DOI：
10.1093/rheumatology/kep034
复制
发表时间：
2009-05-01
期刊：
影响因子：
5.5
通讯作者：
Clancy, Robert M.
中科院分区：
文献类型：
--
作者：
Izmirly, Peter M.;Barisoni, Laura;Clancy, Robert M.
Objective.目的探讨内皮细胞蛋白C受体（endothelial protein C receptor，mEPCR）在狼疮性肾炎（lupus nephritis，LN）肾微血管中的表达，作为判断LN损伤和/或预后的指标。用免疫组化方法分析mEPCR在正常肾脏和49例LN患者的59例活检组织中的表达。在基线、6个月和1年时评估临床参数。mEPCR在所有LN活检组织的髓质、动脉内皮和皮质管周毛细血管（PTC）中均有表达，但在正常肾皮质PTC中无表达。在16/59例活检中观察到25例PTC中的阳性mEPCR染色，并与治疗反应差相关。在25例PTC中，13例mEPCR染色阳性的患者中有11例（84.6例）在6个月随访时对治疗无应答，而在25例PTC中，8/28例（28.6例）mEPCR染色，P 0.0018。1年时，25例PTC中mEPCR染色阳性的12例患者中有10例（83.3例）对治疗无应答（2例进展为终末期肾病），而25例PTC中染色阳性的患者中有8例（33.3例）对治疗无应答，P 0.0116。尽管肾小管间质损伤（TID）总是伴随mEPCR，但该内皮标志物在不存在TID的情况下广泛表达，表明不良反应不能仅归因于TID增加。mEPCR表达与国际肾脏病学会/肾脏病理学会分级、活动性和慢性指数无关。PTCs中mEPCR表达增加可能是LN治疗反应不良的新标志。
Objective. To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy.Methods. mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year.Results. mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in 25 of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6) of 13 patients with positive staining for mEPCR in 25 of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6) with mEPCR staining in 25 PTCs, P 0.0018. At 1 year, 10 (83.3) of 12 patients with positive mEPCR staining in 25 of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3) with positive staining in 25 of the PTCs, P 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices.Conclusion. Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.