Isolated Donor Specific Alloantibody-Mediated Rejection after ABO Compatible Liver Transplantation

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.     

Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

Refractory Ascites After Liver Transplantation: An Analysis of 1058 Liver Transplant Patients at a Single Center

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.     

复合杂合parkin基因突变家族的不同表型

背景：Parkin基因（PRKN）突变可导致常染色体隐性遗传性早发帕金森病（EOPD）。目的：探讨EOPD白人家族PRKN突变的表现和基因型-表型关系。设计：对EOPD家族的3代20例成员进行基因分析，该家族有4例患者。应用直接基因组DNA测序、半定量聚合酶链反应、实时定量聚合酶链反应以及逆转录酶聚合酶链反应分析以确定PRKN突变。结果：4例早发患者（年龄30—38岁）被确定有PRKN复合杂合突变（T240M和EX5_6缺失），虽然PRKN的杂合T240M和纯合EX5_6缺失突变已有描述，但是据悉，本文为上述复合杂合突变的首次报道。患者的表型为典型常染色体隐性遗传性EOPD的表现，其特征是对左旋多巴治疗有效、相对缓慢的进展和运动障碍。所有杂合突变的基因携带者（T240M或EX5_6缺失）和1例56岁的复合杂合突变女性携带者（T240M和EX5_6缺失）无任何神经系统症状。结论：研究发现，PRKN基因复合杂合突变（T240M和EX5_6缺失）导致一个大的白人家族中4例成员发生常染色体隐性遗传性EOPD。另外1例成员具有相同的突变，比4例患者的平均发病年龄大10岁，并且无本病的临床表现。不完全的外显率对遗传咨询具有暗示作用，并且提示复杂的基因一环境交互作用在PRKN相关EOPD的发病机制中发挥作用。     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.     

Case Report: Second case of a successful pregnancy in maternal isovaleric acidaemia

Summary: A female patient with isovaleric acidaemia had a successful outcome from pregnancy.