Kolbeck P C, Wolfe J A, Burchette J, Sanfilippo F
Transplantation. 1987 Feb;43(2):218-24. doi: 10.1097/00007890-198702000-00011.
Using antibody directed against cyclosporine (CsA-Ab) in an avidin-biotin-complex immunoperoxidase technique on routine formalin-fixed tissue specimens, 46 renal biopsies from CsA-treated renal allograft recipients and 23 biopsies from non-CsA-treated patients were examined to identify staining patterns potentially associated with CsA nephrotoxicity (CsA-NT). All specimens were examined independently in a masked fashion by two pathologists for the intensity of (CsA-Ab) specific staining for each of the four distinct patterns identified: diffuse interstitial staining (DIS, 0-3+); fine granular staining of tubular epithelium (FGS, 0-3+); coarse granular staining of tubular epithelium (CGS, 0-3+); and dark cellular staining of mononuclear inflammatory cells (DCS, 0-3+). Based on standard clinical criteria all CsA-treated patients were categorized according to the degree of CsA nephrotoxicity (grades 1-4). Significant differences in the intensity of CsA-Ab labeling were found for three of the four immunohistologic grading patterns (DIS, FGS, DCS). For the DIS and FGS patterns, cases with clinical evidence of moderate-severe CsA-NT (grades 3 and 4) had significantly higher average staining than either the slight-mild CsA-NT cases (grade 1 and 2) or the control cases (grade 0). The DCS pattern demonstrated significantly more staining in the moderate-severe CsA-NT cases than in the controls. The sum of individual scores for the DIS, FGS, and DCS immunohistologic pattern (CsA index) was also significantly higher in the moderate-severe CsA-NT cases (3.57 +/- 0.44) than in either the controls (1.73 +/- 0.23, P less than 0.05) or the slight-mild CsA-NT cases (1.98 +/- 0.27, P less than 0.05), demonstrating a specificity of 78% for identifying moderate-severe CsA nephrotoxicity. The extent of infiltration by Leu 2 (CD8; T cytotoxic-suppressor phenotype) positive cells was not significantly different between the moderate-severe versus the slight-mild CsA-NT outcome groups. However, when CsA index values were used in combination with the intensity of Leu-2-positive cell infiltrates to predict CsA-NT (CsA-treated patients with high CsA-Ab staining as well as low levels of Leu-2-positive infiltrate) the specificity for identifying moderate-severe CsA-NT was 96%. These results suggest that CsA labeling of renal allograft biopsies may be useful for identifying CsA-NT, especially when considered with the nature of inflammatory cell infiltration.
采用抗环孢素抗体（CsA-Ab），运用抗生物素蛋白-生物素复合物免疫过氧化物酶技术，对常规福尔马林固定的组织标本进行检测。对46例接受环孢素治疗的肾移植受者的肾活检标本以及23例未接受环孢素治疗患者的活检标本进行检查，以确定可能与环孢素肾毒性（CsA-NT）相关的染色模式。两名病理学家以盲法独立检查所有标本，观察四种不同模式下（环孢素抗体）特异性染色的强度：弥漫性间质染色（DIS，0 - 3+）；肾小管上皮细胞细颗粒染色（FGS，0 - 3+）；肾小管上皮细胞粗颗粒染色（CGS，0 - 3+）；单核炎症细胞深染（DCS，0 - 3+）。根据标准临床标准，所有接受环孢素治疗的患者按照环孢素肾毒性程度（1 - 4级）进行分类。在四种免疫组织学分级模式中的三种（DIS、FGS、DCS）中，发现环孢素抗体标记强度存在显著差异。对于DIS和FGS模式，有中度至重度环孢素肾毒性临床证据（3级和4级）的病例，其平均染色显著高于轻度至中度环孢素肾毒性病例（1级和2级）或对照组病例（0级）。DCS模式显示，中度至重度环孢素肾毒性病例的染色明显多于对照组。中度至重度环孢素肾毒性病例中，DIS、FGS和DCS免疫组织学模式的个体评分总和（环孢素指数）也显著高于对照组（1.73±0.23，P<0.05）或轻度至中度环孢素肾毒性病例（1.98±0.27，P<0.05），显示出识别中度至重度环孢素肾毒性的特异性为78%。中度至重度与轻度至中度环孢素肾毒性结局组之间，Leu 2（CD8；细胞毒性抑制性T细胞表型）阳性细胞的浸润程度无显著差异。然而，当将环孢素指数值与Leu-2阳性细胞浸润强度结合起来预测环孢素肾毒性时（环孢素治疗患者中环孢素抗体染色高且Leu-2阳性浸润水平低），识别中度至重度环孢素肾毒性的特异性为96%。这些结果表明，肾移植活检中环孢素标记可能有助于识别环孢素肾毒性，特别是结合炎症细胞浸润的性质考虑时。
