Clinical Investigation Of The Serum Soluble CD30 In Chronic Rejection After Kidney Transplantation

In recent 20 years,with the widely using of new kinds of immune suppressants and improving of HLA matching,acute rejection after renal transplantation have been well controlled,while long-term renal graft survival still have not been increased significantly.Under the grim situation of worldwide organs shorting,it is an importment study and an urgent task of transplatation workers to improve graft survival longer.Chronic rejection is an important cause of late allograft dysfunction.Cell immunity has been recognized in all kinds of allograft rejections,in 2003, Pro.Terasaki emphasized the theory of humoral immunity again,the effect of humoral immunity on all kinds of allograft rejections has been thought highly increasingly.Nowadays,it is a common understanding that cell immunity and humoral immunity all play important roles in allograft rejections.Baff meetings of allograft pathology diagnostics has been replenished the antibody mediation rejection into the standards.No matter cell immunity or hummoral immunity,it is no doubt that they all take part in chronic rejection.Therefore,it is vital for us to evaluate the recipients immunity state and diagnose the chronic rejection at early stage.Although there are many kinds methods to detect the recipients immunity state,these indexes all have their limitations to the whole recipients immunity system.For exemple,the detect of T lymph cell CD4/CD8 may reflect the recipients T lymph cell immunity state, but it can't tell us the information about humoral immunity.Another exemple is panel reactive antibody(PRA),it has been used to reflect the humoral immunity for many years and its clinical value has been admitted by us all,but for many many PRA negative recipients,it can not tell us the risk when the renal transplantations will be carried out.The allograft biopsy and pathological check including the C4d depsit in peritubular capillaries(PTC) is the gold standard for all kinds rejetion diagnostic,C4d is a degradation product of complement factor C4 during the classic complement pathway activated by antigen-antibody reaction and its doposit in renal graft tissure of peritubular capillaries is an established maker of humoral response in recipent,and the Banff schema has already admitted it as one of standards,but biopsy is an invasive method for recipients and allografts,so the recipients always don't accept this diagnostic method even if the allograft function has been damaged by unknown reasons.So,it is a very immportant and impending task for us to find some noninvasive and comprehansive indexes to lean about the recipients' immunity state.Mosmann et al classified the mouse T-helper(Th) lymph cells into Th-1 type and Th-2 type according to the cytokines and its funtion in 1986,Th1 lymph cells can secret IFN-γ,IL-2和TNF-βand promote cell immunity,Th2 lymph cells can secret IL-4,IL-5,IL-6,IL-10,IL-13 and promote humoral immunity.In 1991, Maggi et al demonstrated that human Th lymph cells also classified into Th-1 type and Th2-type according to the cytokines and its funtion,and two kinds Th lymph cells could secrete IL-2.Th2 lymph cells has the membrane antigen CD30,and Thl lymph cells has no CD30.CD30 positive Th2 lymph cells can promote two kinds immunity reaction by secrete IL-2 and so on,so the CD30 level can comprehansive reflect the recipients immunity state.The sCD30 molecule,a member of the tumor necrosis factor/nerve growth factor receptor superfamily was originally identifed as a cell surface antigen on Hodgkin's and Reed Sternberg cells and is preferentially expressed on human CD4+ and CD8+T cells that secrete Th2-type cytokines.No or low CD30 expression was found on Th1-type cytokine-secreting T cells.A soluble form of CD30(sCD30) is released into the bloodstream after activation of CD30+T cells.In diseases such as multiple sclerosis in which Th1-type immune responsese predominate,elevated sCD30 serum levels correlated with disease remission,In diseases in which Th2-type immune responses predominate,such as lupus erythematosus or atopic dermatitis, elevated serum sCD30 was associated with increased disease activity.Furthermore, increased serum sCD30 in the early stages of HIV infection predicted a rapid progress in acquired immunodeficiency syndrome.In recent years,sCD30 has been studied that it is closely related to acute rejection and the outcomes of allografts,but there has no reports about the relationship between sCD30 and chronic rejection.Based on CD30~+T cells immunity mechanism,which includes cell and humoral immunity,and there are many unknown specific principles that need us to study,our present study investigated whether increased serum levels of sCD30 could diagnose the chronic rejection in kidney allograft,and by contrasting the indexes of PRA,C4d,we wanted to demonstrate that sCD30 was a comprehansive useful and noninvasive index for chronic rejection diagnosis.Objective:To study the relationship between sCD30 and chronic rejection,and by contrasting the indexes of sCD30,PRA and C4d,we wanted to denmonstrate that sCD30 was a comprehansive useful and noninvasive index for chronic rejection diagnosis.Methods:The first part:all recipients were from the Zhujiang Hospital of the Southern Medical University,and the renal transplant operation had been passed over one year, according to Banff pathology diagnostic standards,36 recipients were chronic rejection group(CR),and 106 recipients who had normal allografts function were selected into the control group.The blood samples of chronic group were collected while the allografts were biopsied,and the blood samples of the control group were taken randomly when the recipients came to check at our outpatient. Firstly,we detected sCD30 by the means of ELISA,then retrospectively analyzed the difference of sCD30 levels between the CR group and the control group.The statistical method was"t"test between two separate samples,The difference was significant when P≤0.05.The second part:36 cases in the CR group were all undergone allografts biopsy, and the allograft's tissue were detected C4d by immunohistochemisty method,and at the same time the PRA were tested again,we retrospectively analyzed the differences of sCD30 levels between the PRA or C4d positive group and negative group.The statistical method were"t"test and"x~2"test between two separate groups.The difference was significant when P≤0.05.Results:1.The relationship between serum sCD30 level and chronic rejection.There were no significant differences in clinical features except gender between the CR group and the control groupThere was significant difference in sCD30 levels between the CR group and the control group,the CR group sCD30 was(193.14±18.63) U/ml,the control group sCD30 was(65.45±19.12) U/ml,the statistic values were(t=34.982,P =0.000)。According to ROC curve analyse,serum sCD30 critical piont of statistical value is 135.50U/ml.2.The relationship between serum sCD30,PRA and C4d.Among the 36 cases in CR group,15 cases were PRA negative and 21 cases were PRA positive,there was no significant difference of sCD30 levels between PRA negative and PRA positive groups.Respectively,the sCD30 were PRA(-) (191.13±19.11) U/ml and PRA(+)(194.57±18.62) U/ml(t=0.540 P=0.593＞0.05).Similarly,17 cases were C4d negative and19 cases were C4d positive among the 36 cases in CR group,there was no significant difference of sCD30 levels between the two groups.Respectively,the sCD30 were C4d(-)(190.24±16.27)U/ml and C4d(+)(195.74±20.61) U/ml,(t=0.515,P=0.608＞0.05).The further analyse of CR group,PRA(+) ratio was 58.3%(21/36), C4d(+) ratio was 52.8%(19/36),between the PRA positive rate of C4d(+) and that ofC4d(-),there was significant difference(84.2%vs 29.4%,x~2=11.085,P= 0.001)。According to the risk analyse between postopration PRA and chronic rejection in all 142 cases,compared the PRA positive cases to the PRA negtive cases, the optimistic ratio of chronic rejetion was 5.35,and the 95%confident interval was (2.37,12.04)。but the sensitivity and specificity of judgement on chronic rejection were only 58.3%and 79.2%,the total accurate rate is 73.9%(105/142)。Conclusions:(1)Abnormal elevated postoperation serum sCD30 is associated with chronic rejection,it is helpful for us to determine and predict the chronic rejetion that is happening.And our investigation may provide clinical data about sCD30 critical point.(2)Compared to PRA,serum sCD30 is relatively comprehansive in detecting chronic rejection and we have not observed the humoral influence on it. And compared to allograft biopsy and C4d test,serum sCD30 detection is noninvasive importantly.