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Detection And Clinical Significance Of The Complement Degradation Product C4d In Acute Rejection In Renal Allografts

Posted on:2004-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:W Q XieFull Text:PDF
GTID:2144360092490721Subject:Surgery
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Medical School, Zhejiang University Postgraduate Xie WenqingSupervisor Prof. Chen JianghuaIntroductionWith the maturity of the technique of renal transplantation, now it becomes the best way to treat end stage renal disease (ESRD), but the loss of renal allograft always is the biggest obstacle in these patients. Acute rejection (AR) is the most important threat to transplanted kidneys in the early phase after transplantation. The signs of AR are deterioation of graft function, fever and the decrease of uric volume. Among them, the deterioation of graft function is the most important. But the definitude of AR needs pathological diagnosis. In clinic, the treatment to AR is classified into two categories: the first one is anticellular rejection such as OKT3, ATG, the second is antihumoral rejection such as plasmapheresis or intravenous immune globulins. The basis of treatment is on the pathological diagnosis. The criterion of pathological diagnosis is based on Banff 97. In Banff 97, rejection is divided into acute vascular rejection (AVR), acute cellular rejection (ACR) and hyperacute rejection (HAR). AR is morphologically characterized by the presence of mononuclear cells in the interstitial compartment, tubulitis, transplant endarteritis, or glomerulitis. But AVR is not equal to acute humoral rejection. It's wrong that ACR or suspicious of rejection (borderline changes) haven't humoral component. In clinic, the patients of ACR orsuspicious of rejection were treated with steroid, ATG or okt3, the prognosis of a subgroup of these patients is poor. It let me think of that these rejections may include humoral components. So many researchers want to find a useful marker that can reflect the humoral component in AR. The start of research aims at the globulins such as IgG, C3, C4, C1q. But at the same time, they find that these indexes haven't usefulness in the diagnosis of acute humoral rejection. A new perspective opened up when Feucht et al pioneered worked on C4d, a component split product that can be detected in renal allografts. C4d is a degradation product of the complement factor C4, which is typically activated during the classical component cascade. Another important step was the demonstration by Collins et al that staining of allograft biopsies for the fragment C4d is specific and reliable method for identifying lesions due to humoral immunity. Now the research on C4d becomes popular. In our study, Emphasis was placed on the relation between the C4d and pathological diagnosis and the significance on predicting prognosis and treatment.AimsThe aim of our study is to establish the technique to detect C4d and know the significance of complement split product C4d in the diagnosis of humoral rejection, At the same time, want to know whether it's a factor that can predict the prognoses of rejection and how to teat such rejection.Materials and MethodOur retrospective analyses include 856 kidney allograft recipients who were transplanted and clinically managed in our center between 1997.12 and 2002.12. We collect 118 cases among them. 116 allografts were of cadaveric origin and 2 from living donars (all first). A total of 136 graft biopsies (102 first, 14 second, 2 third) were examined. Among them, the number of HAR, AYR, ACR, suspicious ofrejection, stable normal function, acute tubular necrosis (ATN) and baseline kidney is 3, 27, 24, 38, 19, 5 and 20 respectively. The complement degradation product C4d was detected by using immunohistochemical technique, the morphological changes were observed in tissue section.Results1. The significance of diagnosis of C4d in AR.The expression of C4d is in all biopsies (3/3) of hyperacute rejection. 77.8% (21/27) biopsies of AYR expressed positive (compared with the group of ACR, suspicious of rejection, stable normal function, ATN, baseline kidney: p<0.01). The expression of C4d in the group of ACR and suspicious of rejection is 37.5%(9/24) and 23.7 (9/238) respectively. But in the group of stable normal function, ATN...
Keywords/Search Tags:C4d, kidney transplantation, acute humoral rejection, prognosis, Immunohistochemistry
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