Izmirly Peter M, Barisoni Laura, Buyon Jill P, Kim Mimi Y, Rivera Tania L, Schwartzman Julie S, Weisstuch Joseph M, Liu David T, Bernstein Stephen, Tseng Chung-E, Belmont Howard M, Esmon Charles T, Merrill Joan T, Askanase Anca D, Thomas David B, Clancy Robert M
Department of Medicine, Division of Rheumatology, New York University School of Medicine, NY, USA.
Rheumatology (Oxford). 2009 May;48(5):513-9. doi: 10.1093/rheumatology/kep034. Epub 2009 Mar 13.
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.
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.
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 < or =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 < or =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.
Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.
研究狼疮性肾炎（LN）患者肾微血管中内皮蛋白C受体（mEPCR）的膜表达情况，将其作为损伤的潜在标志物和/或治疗反应的预后指标。
采用免疫组织化学方法分析正常肾脏以及49例LN患者的59份肾活检组织中mEPCR的表达情况。在基线、6个月和1年时评估临床参数。
在所有LN肾活检组织的髓质、动脉内皮和皮质肾小管周围毛细血管（PTC）中均检测到mEPCR表达，而正常肾脏的皮质PTC中未检测到。59份活检组织中有16份（>25%的PTC中mEPCR染色呈阳性），且与治疗反应不佳相关。在6个月的随访中，13例>25%的PTC中mEPCR染色呈阳性的患者中有11例（84.6%）对治疗无反应，而在≤25%的PTC中mEPCR染色的患者中这一比例为8/28（28.6%），P = 0.0018。1年时，12例>25%的PTC中mEPCR染色呈阳性的患者中有10例（83.3%）对治疗无反应（其中2例进展为终末期肾病），而在≤25%的PTC中染色呈阳性的患者中这一比例为8/24（33.3%），P = 0.0116。虽然肾小管间质损伤（TID）总是伴有mEPCR表达，但在无TID时该内皮标志物也广泛表达，这表明治疗反应不佳不能仅归因于TID增加。mEPCR表达与国际肾脏病学会/肾脏病理学会的分级、活动度和慢性指数无关。
PTC中mEPCR表达增加可能是LN治疗反应不佳的一种新标志物。
