肝移植排斥反应中C4d的表达意义
卜宪敏, 郑智勇, 余英豪, 曾玲, 南京军区福州总医院病理科 福建省福州市 350025
江艺, 南京军区福州总医院院肝胆外科 福建省福州市 350025
卜宪敏, 女, 1980-03-10生, 山东省济宁市人, 汉族. 2003级福建医科大学硕士研究生, 研究方向为病理图象的计算机分析.
通讯作者: 郑智勇, 350025, 福建省福州市西二环北路156号, 南京军区福州总医院病理科. zzy@public.fz.fj.cn
电话: 0591-24937095 传真: 0591-83717703
, 百拇医药 收稿日期: 2005-03-31 接受日期: 2005-04-09
Signification of C4d deposition in liver rejection
Xian-Min Bu, Zhi-Yong Zheng, Ying-Hao Yu, Ling Zeng, Yi Jiang
Xian-Min Bu, Zhi-Yong Zheng, Ying-Hao Yu, Ling Zeng, Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, Fujian Provice, China
Yi Jiang, Department of Hepatobiliary Surgery, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, Fujian Provice, China
, 百拇医药
Correspondence to: Zhi-Yong Zheng, Department of Pathology, Fuzhou General Hospitial of Nanjing Military Command, 156 Xi'erhuan Road, Fuzhou 350025, Fujian Provice, China. zzy@public.fz.fj.cn
Received: 2005-03-31 Accepted: 2005-04-09
Abstract
AIM: To investigate the location and significance of C4d deposition in liver rejection.
, http://www.100md.com
METHODS: Immunohistological staining was performed to observe C4d deposition in the liver allografts biopsies as well as its relationship with the pathological alteration of liver.
RESULTS: C4d expression was 69.2% in the samples of liver cellular rejection, 33.3% in hepatitis B relapse after transplantation and 28.6% in hepatitis B. In the biopsies of liver rejection, C4d was found depositing on the vascular walls of portal areas and hepatic sinusoidal walls. In the biopsies of hepatitis B relapse after transplantation and hepatitis B, C4d deposited only in the vascular walls of portal area. In the biopsies of ischemia reperfusion damage, C4d deposition was observed on the vascular walls of portal areas and hepatic sinusoidal wall in 1 of 12 patients, and follow-up biopsy after 1 month revealed an acute cellular rejection. No C4d deposition was observed in bile duct occlusion after liver transplantation.
, 百拇医药
CONCLUSION: C4d deposition may be served as a sensitive marker in the diagnosis of liver rejection.
Key Words: C4d; Deposition; Liver rejection
Bu XM, Zheng ZY, Yu YH, Zeng L, Jiang Y. Signification of C4d deposition in liver rejection. Shijie Huaren Xiaohua Zazhi 2005;13(11):1314-1316
摘要
, 百拇医药 目的: 研究肝移植排斥反应中C4d沉积的部位和意义.
方法: 对肝移植患者的肝穿刺标本作C4d免疫组化染色，观察C4d阳性沉积情况与肝脏病理改变的关系.
结果: 急性细胞性排斥反应中的69.2%肝移植标本，在肝小叶汇管区小血管壁及肝血窦壁上有C4d的沉积.33.3%移植后乙肝复发和28.6%乙型肝炎的标本中，仅汇管区小血管壁有C4d的沉积，而无肝血窦壁上C4d的沉积.12例器官保存性损伤的肝标本中1例汇管区小血管壁及肝血窦壁上有C4d的沉积，此例1 mo后再次穿刺发现急性细胞性排异反应.肝移植后胆管阻塞的标本中没有发现C4d的沉积.
结论: C4d在肝血窦壁的沉积可以作为肝移植急性排斥反应鉴别诊断一个比较特异的免疫组化指标.
, http://www.100md.com
关键词: C4d; 沉积; 肝移植排斥反应
卜宪敏, 郑智勇, 余英豪, 曾玲, 江艺. 肝移植排斥反应中C4d的表达意义. 世界华人消化杂志 2005;13(11):1314-1316
:在肝血窦壁的沉积，ABC×400;B: 在汇管区小血管壁的沉积，ABC×200.
图2 乙肝标本C4d在汇管区小血管壁及间质内沉积，ABC×400.
图3 移植肾急性排异反应中C4d在肾小管管周小血管壁的沉积，ABC×200.
3 讨论
, http://www.100md.com
在抗体介导的体液性排异中，补体起着协助和加强免疫的调节作用.体液性排斥反应发生时，补体的经典途径即被激活，被激活的CI蛋白水解为C4d，C4d与周围血管的内皮细胞共价结合，所以能够比较持久存在，从而可作为排异时存在体液成分激活的标志[6].移植肾肾小管周围的毛细血管壁C4d沉积是排异反应的一项较特异免疫组化指标[2，6，9-10].本组观察表明，肝移植急性细胞性排斥反应时同样也会出现类似的现象，即C4d在肝血窦壁上的沉积可以用来判别是否出现肝移植急性细胞排异反应.与移植肾急性排异反应相比，肝移植急性排斥反应时肝血窦壁C4d沉积的阳性反应较弱，但明确存在.肝移植急性细胞性排斥反应时C4d的阳性部位与乙型肝炎不同，移植后乙肝复发和乙型肝炎病例C4d阳性部位主要在汇管区，而肝血窦壁未见到C4d沉积.本组12例器官保存性损伤标本中只有1例同时存在汇管区和肝血窦壁C4d沉积，而此例1 mo后再次穿刺发现急性细胞性排异反应.因此，C4d在肝血窦壁的沉积可能是肝移植急性排斥反应的一个比较特异的免疫组化指标.
, http://www.100md.com
从免疫学观点看，C4d沉积代表着经典途经的补体激活，意味着体液免疫反应出现[6-7].以往的研究认为，机体对移植物的急性排异反应，主要是细胞排异反应[8].但从对移植肾急性排异反应的C4d沉积[9]和本观察结果表明，急性细胞性排异反应过程中可以伴有体液排异反应出现.本研究也证实，肝移植急性排异反应时也存在类似的情况;在作为对照的肝炎病例中也有C4d的沉积，提示乙肝的炎症也与体液免疫有关.在乙肝病例中，C4d的沉积主要在汇管区较多细胞浸润的区域，在肝血窦中没有C4d的沉积.这种沉积并不是在所有的乙肝病例中出现，其原因可能与肝炎的活动性有关.
4 参考文献
1 Bohmig GA, Regele H, Exner M. C4d-positive acute humoral renalallograft rejection: effective treatment
, http://www.100md.com
by immuno-adsorption. J Am Soc Nephrol 2001;12:2482-2489
2 刘志红, 陈书芬, 陈朝红, 曾彩虹, 周虹, 陈劲松, 唐政, 黎磊石. 肾移植急性排斥患者肾组织C4d的沉积及其意义.
肾脏病与透析肾移植杂志 2003;12:415-418
3 Duong Van HuyenJP, Fornes P, Guillemain R, Amrein C, Chevalier P, Latremouille C, CreputC, Glotz D, Nochy D,Bruneval P. Acute vascular humoralrejection in a sensitized cardiac graft recipient: diagnostic value of
, 百拇医药
C4d immunof-luorescence. Hum Pathol 2004;35:385-388
4 Banff schemafor grading liver allograft rejection: an international consensusdocument. Hepatology 1997;25:658-663
5 Krukemeyer MG,Moeller J, Morawietz L, Rudolph B, Neumann U, Theruvath T, Neuhaus P,Krenn V. Description
of B lymphocytes and plasma cells,complement, and chemokines/receptors in acute liver allograft
, http://www.100md.com
rejection. Transplantation 2004;78:65-70
6 Regele H,Bohmig GA, Habicht A, Gollowitzer D, Schillinger M, Rockenschaub S,Watschinger B, Kerjaschki D, Exner
M. Capillary deposition of complement splitproduct C4d in renal allografts is associated with basement membraneinjury
in peritubular and glomerular capillaries:a contribution of humoral immunity to chronic allograft rejection. J Am
, 百拇医药
Soc Nephrol 2002;13:2371-2380
7 章爱斌. 移植物急性排斥反应的发生机制. 国外医学免疫学分册 2004;27:4-7
8 Mauiyyedi S,Pelle PD, Saidman S, Collins AB, Pascual M, Tolkoff-Rubin NE, Williams WW,Cosimi AA, Schneeberger
EE, Colvin RB. Chronic humoral rejection:identification of antibody-mediated chronic renal allograft rejection by
C4d deposits in peritubular capillaries.J Am Soc Nephrol 2001;12:574-582
, 百拇医药
9 Herzenberg AM,Gill JS, Djurdjev O, Magil AB. C4d deposition in acute rejection: anindependent long-term
prognostic factor. J Am Soc Nephrol 2002;13:234-241
10 Collins AB,Schneeberger EE, Pascual MA, Saidman SL, Williams WW, Tolkoff-Rubin N,Cosimi AB, Colvin RB.
Complement activation in acutehumoral renal allograft rejection: diagnostic significance of C4d depositsin
peritubular capillaries. J Am SocNephrol 1999;10:2208-2214
编辑 潘伯荣 审读 张海宁, 百拇医药( 卜宪敏,郑智勇,余英豪,曾 玲,江 艺、)
江艺, 南京军区福州总医院院肝胆外科 福建省福州市 350025
卜宪敏, 女, 1980-03-10生, 山东省济宁市人, 汉族. 2003级福建医科大学硕士研究生, 研究方向为病理图象的计算机分析.
通讯作者: 郑智勇, 350025, 福建省福州市西二环北路156号, 南京军区福州总医院病理科. zzy@public.fz.fj.cn
电话: 0591-24937095 传真: 0591-83717703
, 百拇医药 收稿日期: 2005-03-31 接受日期: 2005-04-09
Signification of C4d deposition in liver rejection
Xian-Min Bu, Zhi-Yong Zheng, Ying-Hao Yu, Ling Zeng, Yi Jiang
Xian-Min Bu, Zhi-Yong Zheng, Ying-Hao Yu, Ling Zeng, Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, Fujian Provice, China
Yi Jiang, Department of Hepatobiliary Surgery, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, Fujian Provice, China
, 百拇医药
Correspondence to: Zhi-Yong Zheng, Department of Pathology, Fuzhou General Hospitial of Nanjing Military Command, 156 Xi'erhuan Road, Fuzhou 350025, Fujian Provice, China. zzy@public.fz.fj.cn
Received: 2005-03-31 Accepted: 2005-04-09
Abstract
AIM: To investigate the location and significance of C4d deposition in liver rejection.
, http://www.100md.com
METHODS: Immunohistological staining was performed to observe C4d deposition in the liver allografts biopsies as well as its relationship with the pathological alteration of liver.
RESULTS: C4d expression was 69.2% in the samples of liver cellular rejection, 33.3% in hepatitis B relapse after transplantation and 28.6% in hepatitis B. In the biopsies of liver rejection, C4d was found depositing on the vascular walls of portal areas and hepatic sinusoidal walls. In the biopsies of hepatitis B relapse after transplantation and hepatitis B, C4d deposited only in the vascular walls of portal area. In the biopsies of ischemia reperfusion damage, C4d deposition was observed on the vascular walls of portal areas and hepatic sinusoidal wall in 1 of 12 patients, and follow-up biopsy after 1 month revealed an acute cellular rejection. No C4d deposition was observed in bile duct occlusion after liver transplantation.
, 百拇医药
CONCLUSION: C4d deposition may be served as a sensitive marker in the diagnosis of liver rejection.
Key Words: C4d; Deposition; Liver rejection
Bu XM, Zheng ZY, Yu YH, Zeng L, Jiang Y. Signification of C4d deposition in liver rejection. Shijie Huaren Xiaohua Zazhi 2005;13(11):1314-1316
摘要
, 百拇医药 目的: 研究肝移植排斥反应中C4d沉积的部位和意义.
方法: 对肝移植患者的肝穿刺标本作C4d免疫组化染色，观察C4d阳性沉积情况与肝脏病理改变的关系.
结果: 急性细胞性排斥反应中的69.2%肝移植标本，在肝小叶汇管区小血管壁及肝血窦壁上有C4d的沉积.33.3%移植后乙肝复发和28.6%乙型肝炎的标本中，仅汇管区小血管壁有C4d的沉积，而无肝血窦壁上C4d的沉积.12例器官保存性损伤的肝标本中1例汇管区小血管壁及肝血窦壁上有C4d的沉积，此例1 mo后再次穿刺发现急性细胞性排异反应.肝移植后胆管阻塞的标本中没有发现C4d的沉积.
结论: C4d在肝血窦壁的沉积可以作为肝移植急性排斥反应鉴别诊断一个比较特异的免疫组化指标.
, http://www.100md.com
关键词: C4d; 沉积; 肝移植排斥反应
卜宪敏, 郑智勇, 余英豪, 曾玲, 江艺. 肝移植排斥反应中C4d的表达意义. 世界华人消化杂志 2005;13(11):1314-1316
:在肝血窦壁的沉积，ABC×400;B: 在汇管区小血管壁的沉积，ABC×200.
图2 乙肝标本C4d在汇管区小血管壁及间质内沉积，ABC×400.
图3 移植肾急性排异反应中C4d在肾小管管周小血管壁的沉积，ABC×200.
3 讨论
, http://www.100md.com
在抗体介导的体液性排异中，补体起着协助和加强免疫的调节作用.体液性排斥反应发生时，补体的经典途径即被激活，被激活的CI蛋白水解为C4d，C4d与周围血管的内皮细胞共价结合，所以能够比较持久存在，从而可作为排异时存在体液成分激活的标志[6].移植肾肾小管周围的毛细血管壁C4d沉积是排异反应的一项较特异免疫组化指标[2，6，9-10].本组观察表明，肝移植急性细胞性排斥反应时同样也会出现类似的现象，即C4d在肝血窦壁上的沉积可以用来判别是否出现肝移植急性细胞排异反应.与移植肾急性排异反应相比，肝移植急性排斥反应时肝血窦壁C4d沉积的阳性反应较弱，但明确存在.肝移植急性细胞性排斥反应时C4d的阳性部位与乙型肝炎不同，移植后乙肝复发和乙型肝炎病例C4d阳性部位主要在汇管区，而肝血窦壁未见到C4d沉积.本组12例器官保存性损伤标本中只有1例同时存在汇管区和肝血窦壁C4d沉积，而此例1 mo后再次穿刺发现急性细胞性排异反应.因此，C4d在肝血窦壁的沉积可能是肝移植急性排斥反应的一个比较特异的免疫组化指标.
, http://www.100md.com
从免疫学观点看，C4d沉积代表着经典途经的补体激活，意味着体液免疫反应出现[6-7].以往的研究认为，机体对移植物的急性排异反应，主要是细胞排异反应[8].但从对移植肾急性排异反应的C4d沉积[9]和本观察结果表明，急性细胞性排异反应过程中可以伴有体液排异反应出现.本研究也证实，肝移植急性排异反应时也存在类似的情况;在作为对照的肝炎病例中也有C4d的沉积，提示乙肝的炎症也与体液免疫有关.在乙肝病例中，C4d的沉积主要在汇管区较多细胞浸润的区域，在肝血窦中没有C4d的沉积.这种沉积并不是在所有的乙肝病例中出现，其原因可能与肝炎的活动性有关.
4 参考文献
1 Bohmig GA, Regele H, Exner M. C4d-positive acute humoral renalallograft rejection: effective treatment
, http://www.100md.com
by immuno-adsorption. J Am Soc Nephrol 2001;12:2482-2489
2 刘志红, 陈书芬, 陈朝红, 曾彩虹, 周虹, 陈劲松, 唐政, 黎磊石. 肾移植急性排斥患者肾组织C4d的沉积及其意义.
肾脏病与透析肾移植杂志 2003;12:415-418
3 Duong Van HuyenJP, Fornes P, Guillemain R, Amrein C, Chevalier P, Latremouille C, CreputC, Glotz D, Nochy D,Bruneval P. Acute vascular humoralrejection in a sensitized cardiac graft recipient: diagnostic value of
, 百拇医药
C4d immunof-luorescence. Hum Pathol 2004;35:385-388
4 Banff schemafor grading liver allograft rejection: an international consensusdocument. Hepatology 1997;25:658-663
5 Krukemeyer MG,Moeller J, Morawietz L, Rudolph B, Neumann U, Theruvath T, Neuhaus P,Krenn V. Description
of B lymphocytes and plasma cells,complement, and chemokines/receptors in acute liver allograft
, http://www.100md.com
rejection. Transplantation 2004;78:65-70
6 Regele H,Bohmig GA, Habicht A, Gollowitzer D, Schillinger M, Rockenschaub S,Watschinger B, Kerjaschki D, Exner
M. Capillary deposition of complement splitproduct C4d in renal allografts is associated with basement membraneinjury
in peritubular and glomerular capillaries:a contribution of humoral immunity to chronic allograft rejection. J Am
, 百拇医药
Soc Nephrol 2002;13:2371-2380
7 章爱斌. 移植物急性排斥反应的发生机制. 国外医学免疫学分册 2004;27:4-7
8 Mauiyyedi S,Pelle PD, Saidman S, Collins AB, Pascual M, Tolkoff-Rubin NE, Williams WW,Cosimi AA, Schneeberger
EE, Colvin RB. Chronic humoral rejection:identification of antibody-mediated chronic renal allograft rejection by
C4d deposits in peritubular capillaries.J Am Soc Nephrol 2001;12:574-582
, 百拇医药
9 Herzenberg AM,Gill JS, Djurdjev O, Magil AB. C4d deposition in acute rejection: anindependent long-term
prognostic factor. J Am Soc Nephrol 2002;13:234-241
10 Collins AB,Schneeberger EE, Pascual MA, Saidman SL, Williams WW, Tolkoff-Rubin N,Cosimi AB, Colvin RB.
Complement activation in acutehumoral renal allograft rejection: diagnostic significance of C4d depositsin
peritubular capillaries. J Am SocNephrol 1999;10:2208-2214
编辑 潘伯荣 审读 张海宁, 百拇医药( 卜宪敏,郑智勇,余英豪,曾 玲,江 艺、)
