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.     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Chronological changes in the complement system in sepsis

The time courses of serum complement levels and the severity of sepsis were compared in two groups of septic patients, one in which the patients survived (surviving group) and one in which they did not (nonsurviving group). The components of the complement system, namely, C3a, C4a, C5a, CH50, C3, C4, and C5, were measured at several points in time after the diagnosis of sepsis had been established. A 2-antibody radioimmunoassay was used to measure C3a, C4a, and C5a; the latex agglutination test was used to measure C3 and C4; nephelometry was used to measure C5; and Meyer's 50% hemolysis method was used to measure CH50. Following the diagnosis of sepsis, the levels of CH50, C3, and C4 were significantly lower in the nonsurviving than the surviving group, while the levels of C3a and C4a were significantly higher in the nonsurviving than the surviving group. The C5a levels were significantly higher in the nonsurviving than the surviving group, although no significant intergroup differences were subsequently noted. These results suggest that the serum levels of C3a, C4a, C5a, CH50, C3, and C4 could serve as indices of the severity of sepsis. Thus, monitoring the complement system may be useful for predicting the outcome of patients with sepsis.     

华支睾吸虫病患者血清中免疫球蛋白和C_3含量的变化

本文分别采用 ELISA 双抗体夹心法和琼脂单向免疫扩散法检测了华支睾吸虫病患者血清中各类免疫球蛋白和 C_3的含量。结果显示:患者血清中 I gG、I gM 和 I gE 的水平明显高于正常对照组,I gA 的水平与正常人相比无明显改变;而 C_3的含量显著低于正常人。提示:人体感染华支睾吸虫病后,I gG、I gM 和 I gE 与相应的特异性抗体呈同步增高的趋势;补体和抗体协同参与华支睾吸虫病的免疫学发病机理,在此过程中消耗补体,使 C_3含量降低。     

Influence of complement on sperm motility

Isolated sperm from normo-, oligo- and astheno-spermic men were incubated for 20 h in medium supplemented with 8% heat-inactivated or untreated human serum, and in medium with heated or untreated serum deficient in complement factor C3. Before and after incubation, sperm motility was assessed by means of a computer-assisted semen analyser. The results did not show significant differences between the motility of sperm incubated in heated or untreated serum. It is concluded that heating of homologous serum is not necessary for preserving sperm motility and in some cases may even be disadvantageous.     

补体对免疫沉淀的抑制作用与小儿肾脏疾病的关系

以辣根过氧化物酶（PO）和抗-PO作为免疫沉淀中的抗原和抗体，用光电比色法，对78例小儿肾脏疾病血清补体对免疫沉淀的抑制作用（IIPC）进行了研究，并同时检测补体成分C3、C4。结果，正常对照IIPCOD值为0．505±0．085，急性肾小球肾炎（0．137±0．108）显著降低（P＜0．001）；慢性肾小球肾炎（0．470±0．053）改变不明显（P＞0．05）；肾病综合征（0．401±0．038）明显低下（P＜0．05）。IIPC低下的发生率依次为急性肾小球肾炎（83％）、肾病综合征（43％）、慢性肾小球肾炎（32％）。表明小儿肾小球疾病时IIPC大多降低并与疾病的活动性有关。因此认为IIPC低下在肾脏病的发生和发展中起一定作用。     

病毒性心肌炎及扩张型心肌病患者心内膜心肌活检标本中免疫球蛋白的检测

对病理学确诊的25例病毒性心肌炎（VMC）和10例扩张型心肌病（DCM）患者心内膜心肌活检标本，运用ABC技术，进行了免疫球蛋白IgG、IgM、IgA和补体C3的检测。结果：20例VMC和9例DCM的标本中，发现了IgG和IgM的沉积，主要分布于心肌肌膜和毛细血管内皮，IgG的肌膜沉积与同步做的病理切片中观察到的心肌细胞坏死和炎性细胞浸润有病理形态学联系。两组患者中均未发现IgA和C3沉积。结果显示，IgG是参与VMC和DCM心肌损伤的主要免疫球蛋白，心肌病变与抗体诱导的免疫反应有关。     

Thrombin Inhibition in discordant xenograft rejection

Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents.     

Plasma C3c in immune-mediated neurological diseases: a preliminary report

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase. Plasma C3c levels were elevated in the group with immune mediated diseases when compared with those of non-immune mediated diseases. The sensitivity and specificity of C3c as a diagnostic test for immune mediated neurological diseases were 61.4 and 100% respectively with a positive and negative predictive value of 100 and 41%. the C3c levels in plasma correlated well with disease severity in MG and GBS patients. Such a correlation was also evident in all CIDP patients except one that had persistent elevation in the presence of clinical improvement. Results suggest that the plasma C3c level may be useful for differentiating immune from non-immune mediated neurological diseases. Plasma C3c may also be used for monitoring disease severity, particularly in myasthenia gravis.     

放免法检测乙型慢性活动性肝炎病人红细胞C3b受体的研究

用放免法检测乙型慢性活动性肝炎病人的红细胞ｃ３ｂ受体（ＫＢＣＣＲ１）．结果：病人ＲＢＣＣＲ１明显低于献血员（Ｐ＜０．０５）；抗－ＨＢｓ特异性免疫复合物阳性病人ＲＢＣＣＲ１明显低于阴性病人（Ｐ＜０．０１），与红细胞Ｃ３ｂ受体花环试验检测结果一致。表明乙型慢性活动性肝炎病人ＲＢＣＣＲ１数量减少，活性下降。其原因可能是特异性循环免疫复合物占据了ＲＢＣＣＲ１空位，使ＣＲ１活性下降。