Kfoury Abdallah G, Hammond M Elizabeth H, Snow Gregory L, Stehlik Josef, Reid Bruce B, Long James W, Gilbert Edward M, Bader Feras M, Bull David A, Renlund Dale G
LDS Hospital and Intermountain Healthcare, Salt Lake City, Utah 84143, USA.
J Heart Lung Transplant. 2007 Dec;26(12):1264-9. doi: 10.1016/j.healun.2007.09.011. Epub 2007 Nov 26.
The International Society for Heart and Lung Transplantation (ISHLT) recently established a diagnostic scheme for antibody-mediated rejection (AMR). Currently, however, confirmatory immunohistochemistry studies are recommended only if AMR is clinically or histologically suspected. In this study, we examine whether a pattern of repetitive AMR occurred early enough after transplantation to warrant prospective immunohistochemistry screening in all recently transplanted recipients.
We queried our pathology database of adult and pediatric endomyocardial biopsies (EMBs) from 1985 to 2005. All EMB specimens were prospectively studied by immunofluorescence in the early post-operative period. AMR was defined as the presence of complement and immunoglobulin deposits on frozen section. Only patients classified as antibody-mediated rejectors (>or=3 episodes of AMR) were included. Cumulative incidence and time from transplant to first and third AMR episodes were obtained.
Three hundred seventy-five of 870 heart transplant recipients had >or=3 episodes of AMR. Mean age of recipients was 45.6 years and 78% were male. A total of 19,569 EMBs comprised the study data. By 100 days post-transplant, 85% of patients had their first and 54% their third AMR. In addition, patients showed a clear trend of early clustering of AMR-positive biopsies. Results were similar regardless of whether or not muromonab-CD3 (Orthoclone OKT3) induction was used.
We advocate early immunohistochemical surveillance testing for AMR to supplement the diagnostic algorithm established by the ISHLT, because a pattern of AMR becomes manifest soon after transplantation. This change will allow earlier detection of asymptomatic AMR and may prompt changes in immunosuppression strategies to avoid adverse outcomes.
国际心肺移植学会（ISHLT）最近制定了抗体介导排斥反应（AMR）的诊断方案。然而，目前仅在临床或组织学上怀疑存在AMR时才建议进行确证性免疫组织化学研究。在本研究中，我们探讨了移植后早期是否出现反复性AMR模式，从而有必要对所有近期移植受者进行前瞻性免疫组织化学筛查。
我们查询了1985年至2005年成人及儿童心内膜心肌活检（EMB）的病理数据库。所有EMB标本在术后早期均进行了前瞻性免疫荧光研究。AMR定义为冰冻切片上存在补体和免疫球蛋白沉积。仅纳入被分类为抗体介导排斥反应者（≥3次AMR发作）。获得累积发病率以及从移植到首次和第三次AMR发作的时间。
870例心脏移植受者中有375例出现≥3次AMR发作。受者的平均年龄为45.6岁，78%为男性。共有19569次EMB构成研究数据。移植后100天时，85%的患者出现首次AMR，54%的患者出现第三次AMR。此外，患者显示出AMR阳性活检早期聚集的明显趋势。无论是否使用莫罗单抗-CD3（Orthoclone OKT3）诱导，结果相似。
我们主张对AMR进行早期免疫组织化学监测检测，以补充ISHLT制定的诊断算法，因为AMR模式在移植后不久就会显现。这一改变将使无症状AMR得以更早检测，并可能促使免疫抑制策略的改变以避免不良后果。
