D'Errico A, Corti B, Pinna A D, Altimari A, Gruppioni E, Gabusi E, Fiorentino M, Bagni A, Grigioni W F
Policlinico S. Orsola-Malpighi, Instituto Felice Addarii, Viale Ercolani 4/2, Bologna 40138, Italy.
Transplant Proc. 2003 Dec;35(8):3061-5. doi: 10.1016/j.transproceed.2003.10.073.
In human heart and kidney transplantations, granzyme B (GrB) and perforin have both been shown to be predictive markers for acute cellular rejection (ACR). We investigated the tissue expression and possible relationship of GrB and perforin to the clinical outcome, histopathology, and function of intestinal transplants. In 13 consecutive patients undergoing small intestine transplantation, histologic/immunohistochemical rejection monitoring was performed together with GrB and perforin immunostaining (score "0", 0%-10% positive lymphocytes; "1", 10%-25%; "2", 25%-50%; "3", >50%). Eleven patients are currently alive and well. All 11 had at least one episode of ACR: one patient had 6 episodes of severe ACR requiring retransplantation; the remaining 10 experienced only mild or moderate rejection. Both GrB and perforin were always co-expressed. A highly significant correlation was observed between GrB/perforin scores and histological severity of ACR (Pearson's coefficient, R < 0.0009). Interestingly, score 3 GrB/perforin immunostaining was recorded only in the context of severe ACR; all the histologically negative or "indeterminate" biopsies (n = 6) taken from a single affected patient showed GrB/perforin scores of 1 or 2. By contrast, none of the other tested histologically negative/"indeterminate" biopsies (n = 350), including those performed during graft stabilization, had raised GrB or perforin scores. We conclude that in intestinal transplantation recipients, a direct correlation seems to exist between histologically confirmed ACR and raised GrB/perforin immunohistochemical scores. Our findings suggest the need to investigate the possibility of predicting ACR by routine serum polymerase chain reaction (PCR) monitoring, which would reduce discomfort to patients.
在人体心脏和肾脏移植中，颗粒酶B（GrB）和穿孔素均已被证明是急性细胞排斥反应（ACR）的预测标志物。我们研究了GrB和穿孔素在肠道移植中的组织表达及其与临床结局、组织病理学和功能的可能关系。在13例连续接受小肠移植的患者中，进行了组织学/免疫组织化学排斥监测以及GrB和穿孔素免疫染色（评分“0”，阳性淋巴细胞0%-10%；“1”，10%-25%；“2”，25%-50%；“3”，>50%）。目前11例患者存活且状况良好。所有11例患者均至少发生过1次ACR：1例患者发生6次严重ACR，需要再次移植；其余10例仅经历了轻度或中度排斥反应。GrB和穿孔素总是共同表达。观察到GrB/穿孔素评分与ACR的组织学严重程度之间存在高度显著相关性（Pearson系数，R<0.0009）。有趣的是，仅在严重ACR的情况下记录到GrB/穿孔素免疫染色评分为3；从1例受影响患者身上采集的所有组织学阴性或“不确定”活检标本（n = 6）的GrB/穿孔素评分为1或2。相比之下，其他经检测的组织学阴性/“不确定”活检标本（n = 350），包括在移植物稳定期进行的活检，均未出现GrB或穿孔素评分升高。我们得出结论，在肠道移植受者中，组织学确诊的ACR与升高的GrB/穿孔素免疫组织化学评分之间似乎存在直接相关性。我们的研究结果表明，有必要研究通过常规血清聚合酶链反应（PCR）监测预测ACR的可能性，这将减少患者的不适。
