Torrealba Jose R, Samaniego Milagros, Pascual Julio, Becker Yolanda, Pirsch John, Sollinger Hans, Odorico Jon
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792-3224, USA.
Transplantation. 2008 Dec 27;86(12):1849-56. doi: 10.1097/TP.0b013e3181902319.
The deposition of the complement split fragment C4d and its association with acute antibody-mediated rejection (AMR) in pancreas transplant (PTx) is not well defined. To characterize the deposition of C4d in PTx, we analyzed 27 PTx biopsies from 18 patients transplanted between 2004 and 2007 at the University of Wisconsin.
The presence of C4d was graded in interacinar capillaries (IAC), islets, interstitium, and small- and medium-size vessels. Sera obtained at the time or within 5 days of the biopsy were tested for antidonor-specific antibodies (DSA).
16 biopsies (59.26%) showed at least 5% C4d+ IAC (range 5%-90%). Of those, five biopsies (18.5%) revealed diffuse labeling (>50% C4d+ IAC) and 11 (40.74%) showed focal staining (5%-50% C4d+ IAC). C4d+ IAC (>5%) was significantly associated with the presence of strong DSA for class I or class II (P<0.018). C4d staining of the media or endothelium of small and medium-size vessels was a common finding in all biopsies without any association with DSA. Similarly, staining of islets and parenchymal interstitium was not statistically associated with AMR. The majority of patients received intravenous corticosteroid bolus and taper, with specific cases requiring thymoglobulin, IVIg, rituximab, or plasmapheresis. Forty-six percent of patients who demonstrated AMR returned to insulin therapy because of chronic graft damage and loss of C-peptide.
Our findings support the potential role of C4d labeling of PTx biopsies in the diagnosis of AMR and emphasize the staining of IAC as a valuable histologic tool for the diagnosis.
补体裂解片段C4d在胰腺移植（PTx）中的沉积及其与急性抗体介导排斥反应（AMR）的关联尚未明确。为了明确C4d在PTx中的沉积情况，我们分析了2004年至2007年在威斯康星大学接受移植的18例患者的27份PTx活检标本。
在腺泡间毛细血管（IAC）、胰岛、间质以及中小血管中对C4d的存在情况进行分级。在活检时或活检后5天内采集的血清检测抗供体特异性抗体（DSA）。
16份活检标本（59.26%）显示至少5%的IAC有C4d阳性（范围为5% - 90%）。其中，5份活检标本（18.5%）显示弥漫性标记（>50%的IAC为C4d阳性），11份（40.74%）显示局灶性染色（5% - 50%的IAC为C4d阳性）。IAC中C4d阳性（>5%）与I类或II类强DSA的存在显著相关（P<0.018）。中小血管的中膜或内皮C4d染色在所有活检标本中均常见，且与DSA无关联。同样，胰岛和实质间质的染色与AMR无统计学关联。大多数患者接受了静脉注射糖皮质激素冲击及逐渐减量治疗，特定病例需要使用抗胸腺细胞球蛋白、静脉注射免疫球蛋白、利妥昔单抗或血浆置换。表现出AMR的患者中有46%因慢性移植物损伤和C肽丧失而恢复胰岛素治疗。
我们的研究结果支持PTx活检标本中C4d标记在AMR诊断中的潜在作用，并强调IAC染色作为一种有价值的组织学诊断工具。
