Troxell Megan L, Higgins John P, Kambham Neeraja
Department of Pathology, Stanford University Medical Center, Stanford, Calif, USA.
Arch Pathol Lab Med. 2006 Oct;130(10):1489-96. doi: 10.5858/2006-130-1489-EOCSIL.
Antibody-mediated humoral rejection in kidney and heart allografts is well recognized and is often associated with poor outcome. C4d deposition in allograft biopsy specimens occurs at sites of antibody-mediated complement activation and has become one of the histopathologic criteria for diagnosis of humoral rejection in the kidney and the heart.
To study immunohistochemical C4d staining as a potential diagnostic marker in liver and small intestine allograft biopsy specimens.
Thirty-six small intestine and 71 liver specimens, including native specimens, allografts with and without histologic features of acute cellular rejection, and explants, were stained with antisera to C4d using an immunohistochemical method on formalin-fixed, paraffin-embedded tissue.
In small intestine, C4d labeled capillaries in 27% of cases with no evidence of rejection, 36% of cases with evidence of acute rejection, and 2 (28%) of 7 specimens of native normal small intestine. In liver allograft biopsy specimens, C4d stained endothelium of veins, arteries, and/or sinusoids in 2 (8%) of 25 cases of acute rejection with central vein involvement; C4d staining was negative in biopsy specimens with no evidence of rejection. C4d stained the endothelium in a subset of explanted liver allografts with ductopenic rejection or chronic vascular rejection and strongly stained 1 explant with features of hyperacute rejection.
The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our data show C4d is unlikely to have utility in small intestine allograft biopsy specimens; however, further study in liver allografts, in conjunction with donor-specific antibody testing, is warranted.
肾和心脏同种异体移植中抗体介导的体液排斥反应已得到充分认识，且常与不良预后相关。同种异体移植活检标本中的C4d沉积发生在抗体介导的补体激活部位，已成为肾和心脏体液排斥反应诊断的组织病理学标准之一。
研究免疫组化C4d染色作为肝和小肠同种异体移植活检标本潜在诊断标志物的情况。
36份小肠标本和71份肝标本，包括原位标本、有或无急性细胞排斥组织学特征的同种异体移植标本以及移植肝切除标本，采用免疫组化方法，用抗C4d抗血清对福尔马林固定、石蜡包埋的组织进行染色。
在小肠中，27%无排斥证据的病例、36%有急性排斥证据的病例以及7份原位正常小肠标本中的2份（28%），C4d标记了毛细血管。在肝同种异体移植活检标本中，25例伴有中央静脉受累的急性排斥病例中有2例（8%），C4d对静脉、动脉和/或肝血窦内皮进行了染色；无排斥证据的活检标本中C4d染色为阴性。C4d在一部分有胆管消失性排斥或慢性血管排斥的移植肝切除标本中对内皮进行了染色，1份具有超急性排斥特征的移植肝切除标本C4d染色强烈。
C4d染色在实体器官移植中的临床应用可能因器官而异。我们的数据表明，C4d在小肠同种异体移植活检标本中不太可能有用；然而，有必要结合供体特异性抗体检测对肝同种异体移植进行进一步研究。
