Clinical Investigation Of The Significance Of C4d In Chronic Rejection After Kidney Transplantation

BackgroundSince allograft renal transplantation got succeed in 1954,clinical practice and base research both obtain great progress. Now the pathogenesis of chronic allograft rejection is not yet identify clearly,as mostly scholar deem it's immunity and nonimmunity mechanism play synergism. For clinicians, therefore, Theruvath believes that the diagnosis of chronic allograft rejection is based on these four following aspects:①progressive rise in serum creatinine over 12 months;②typical pathologic features by light microscopy (transplant arteriopathy and glomerulopathy);③widespread C4d deposits in PTC by immunofluorescence;④detection of 'de novo' DSA at the time of biopsy.According to the humoral theory of transplantation,antibodies cause allograft rejection. Publications are cited showing that antibodies: (1) cause hyperacute kidney rejection, (2) lead to C4d deposits associated with early kidney graft failures, (3) are a good indicator of presensitization leading to early acute rejections,(4) were present in 96% of 826 patients who rejected a kidney graft, (5) are associated with chronic rejection in 33 studies of kidney, heart, lung and liver grafts,and (6) in three studies, appeared in the circulation before evidence of bronchiolitis obliterans in lung transplants, and before kidney rejection. In addition,a prospective cooperative study of 1629 patients in 24 centers demonstrated that antibodies foretold subsequent failures after a follow-up period of 6 months(p = 0.05). The specificity of antibodies detected inthe serum of rejecting patients were often not donor specific, presumably because they were absorbed by the rejecting organ.Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection.Objective:Detect allogragt tissue ofpatients with chronic rejection,to explore the clinical significance of C4d deposition in peritubular capillaries.Object and methods:1. ObjectForty renal allograft biopsies with chronic rejection after renal transplantation comprise twenty one males and nineteen females. Their mean age is 38.5±7.6 years.2.Method2.1 Detected C4dIn this study,renal allograft biopsies was examined immunohistochemically for endothelial deposition of C4d as surrogate marker antibody-mediated alloreactivity in renal allografts. 2.2 Detected PRATaked 10ml blood of patients,used ELISA to detect PRA,and then used software to analyse the final result.2.3 Groups(1)C4d_PTC-positive group: Positive staining is defined as bright linear staining along capillary basement membranes typically involving over half of sampled capillaries.(2)C4d_PTC-negative group:C4d may detected in Glomerular mesangium, glomerular basement membrane and tubule basement membrane,but not in peritubular capillaries.3. Statistical analysis: SPSS 11.5 statistical soft was used. The data was shown as ((x|-)±s) ,the measurement data was tested by independent-samples t-test , the numeration data was tested by crosstabs, P≤0.05 has statistical significance.Results:1.Positive staining is defined as bright linear staining along capillary basement membranes typically involving over half of sampled capillaries. 13 of the 40 index biopsies (32.5%) showed linear C4d deposition along endothelial cells of PTC and C4d may detected in Glomerular mesangium, glomerular basement membrane and tubule basement membrane,but not in peritubular capillaries. Moreover, 19 of 40 blood serum(47.5%)were PRA positive.2.In C4d_PTC-positive group , we detected 52.6% of PRA positive versus 47.4% of PRA negative examples. In contrast, there were 14.3% of PRA positive versus 85.7% of PRA negative examples in C4dPTC-negative group. The difference was statistically significant (P <0.05).3.In C4d_PTC-positive group,we found 6 males versus 7 females, but in C4d_PTC-positive group, there were 15 males versus 12 females, the difference was not statistically significant in gender(P>0.05);However, the mean age was 38.2±12.7 in C4d_PTC-positive group versus 39.2±11.1 in C4d_PTC-negative group, the difference was not statistically significant in years of age(P>0.05); In history of pregnancy, C4d_PTC-positive group has more number of pregnancy than C4d_PTC-negative group (85.7% versus 66.7%), the difference was statistically significant (P<0.05); In number of transplantation, the former group has 4 patients with two transplantation and 1 patient with three transplantation,the latter group just has 1 patient with two transplantation, the difference was statistically significant (P<0.05).In warm ischemia time, there was 6. 45±2. 43minutes in C4d_PTC-positive group versus 6. 26±1.55minutes in C4d_PTC-negative group, the difference was not statistically significant (P>0.05);In contrast,the cold ischemia time was 10. 19±2. 20hours in former group versus 9.71±1.78hours in latter group, the difference was not statistically significant (P>0.05);In anti-rejection project after renal transplantation, all patients treated with CsA/FK506,MMF and prednisone.Conclusion:1. Peritubular capillary deposition of C4d is connect with PRA in blood serum, the C4d deposition rate is obviously higher than negative group in patients with PRA positive.2. Humoral immune is a significance factor in allograft function decrease,since PRA level is obviously increase in patients with chronic rejection.3. C4d is a useful marker in chronic humoral rejection after renal transplantation.For some patients with creeping creatinine,take a biopsy to detect C4d as soon as possible and therapeutic measure,may prevent proceed and development of chronic humoral rejection.