Holt Dudley B, Liapis Helen, Mohanakumar Thalchallour, Phelan Donna R, Gandi Sanjiv K, Huddleston Charles B, Canter Charles E
Departments of Pediatrics, Pathology and Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1014, USA.
J Heart Lung Transplant. 2008 Oct;27(10):1073-8. doi: 10.1016/j.healun.2008.07.013.
Pediatric heart transplant recipients with a positive complement-dependent cytotoxic (CDC) donor-recipient crossmatch are at high risk for rejection. We sought to correlate the pattern of C3d and C4d myocardial capillary deposition and pericapillary macrophage infiltration, possible markers of antibody-mediated rejection, to clinical evidence of rejection in these patients.
Were studied 15 pre-sensitized pediatric patients who had 21 rejection episodes, as defined by International Society for Heart and Lung Transplantation (ISHLT) biopsy Grade >or=2R and/or the development of abnormal left ventricular (LV) function at >1 week after transplant. Archived paraffin-embedded endomyocardial biopsies (n = 74) from these patients were subjected to immunoperoxidase staining for C3d, C4d and CD68 in duplicate. Positive and negative controls were included for each assay.
C3d deposition was present in 74 of 74 (100%) specimens. C4d deposition was present in 6 of 74 (8%) biopsies from 4 patients. Biopsies with C4d deposition had ISHLT Grade >or=2R cellular infiltration in 5 of 6 specimens. Pericapillary macrophage infiltration, defined as positive staining for CD68, was found in 34 of 74 (46%) biopsies, and was associated with ISHLT Grade >or=2R in 10 of 34 (29%).
C3d deposition was universally present after heart transplantation with a CDC(+) donor/recipient crossmatch. C4d deposition and pericapillary macrophage infiltration were found with some, but not all, episodes of rejection. Further study is needed to understand the significance of the presence of complement fragments and pericapillary macrophage infiltration in these endomyocardial biopsies.
补体依赖细胞毒性（CDC）供受者交叉配型呈阳性的小儿心脏移植受者发生排斥反应的风险很高。我们试图将C3d和C4d心肌毛细血管沉积模式以及毛细血管周围巨噬细胞浸润（抗体介导排斥反应的可能标志物）与这些患者排斥反应的临床证据相关联。
研究了15例预先致敏的小儿患者，他们有21次排斥反应发作，根据国际心肺移植学会（ISHLT）活检分级≥2R和/或移植后1周以上左心室（LV）功能异常来定义。对这些患者存档的石蜡包埋心内膜活检标本（n = 74）进行一式两份的C3d、C4d和CD68免疫过氧化物酶染色。每次检测均包括阳性和阴性对照。
74份标本中有74份（100%）存在C3d沉积。74份活检标本中有6份（8%）来自4例患者的标本存在C4d沉积。有C4d沉积的活检标本中，6份标本中有5份ISHLT分级≥2R细胞浸润。74份活检标本中有34份（46%）发现毛细血管周围巨噬细胞浸润，定义为CD68染色阳性，其中34份中有10份（29%）与ISHLT分级≥2R相关。
在CDC（+）供受者交叉配型的心脏移植后，C3d沉积普遍存在。在部分但并非所有排斥反应发作中发现了C4d沉积和毛细血管周围巨噬细胞浸润。需要进一步研究以了解这些心内膜活检中补体片段和毛细血管周围巨噬细胞浸润的意义。
