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Abstract Summary & Conclusion SUMMARY & CONCLUSION This is a retrospective study on 92 needle biopsies of 61 patients who have been transplanted during period (January 1995 and December 1996). Fifty patients were male and eleven patients were female with mean age 30.4 ±13. These biopsies were re-diagnosed and reclassified histologically according to Banff (97) classification. 40 were diagnosed as borderline changes, 30 were diagnosed as type I rejection, 18 were diagnosed as type II rejection and 4 were diagnosed as type III rejection. Also immunohistochemical stalnlng were done for these 92 biopsies using six monoclonal antibodies (CD45, CD4, COB,CD68, CD57 and CD74) to analyse interstitial inflammatory infiltrate. Acute cellular rejection remains a major problem in the management of patients during the early phase after renal transplantation (Erren et al., 1999) .. Acute rejection is the most significant variable in renal allograft survival and function (Palomar et al., 1999). The core of needle biopsy is the gold standard by which establish the correct diagnosis of clinically apparent renal allograft dysfunction (Waiser et al., 2000). So, standardization of renal allograft biopsy interpretation is necessary to determine the most sensitive and specific pathologic findings to diagnose the extension and severity of rejection. Also, to guide therapy in transplant patients and to establish an objective end point for clinical trails of new antirejection drugs (Racusen et al., 1996, and Palomar et al., 1999). A series of meeting at Banff were introduced an international standard for evaluation of biopsies after renal transplantation. This allowed classification of renal allograft pathology and acute rejection in particular. The goal of the Banff classification of renal allograft rejection was a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. -132- -- ._.----” ..- - ._.~.- ------_. --- ._--- Summary & Conclusion The Banff (97) working classification is the modification of two classifications that are most widely used in diagnosis of renal allograft pathology [Banff (93-95) working classification and Collaporative Clinical Trails in Transplantation (CCTT)]. This study confirm a significant association between histologic grading for acute rejection according to the new revised Banff (97) classification and graft survival (P value 0.01). Also we demonstrate that among the specific pathologic lesions the presence of vasculitis (intimal arteritis), but not severity of glomerulitis and tubulitis or extent of interstitial inflammation, was the only predictor of a poor graft survival (P value 0.006). Immunohistochemical analysis of the interstitial inflammatory cellular infiltrate gives the chance to more accurate recognition and phenotype these mononuclear cells in renal biopsy specimens during acute rejection. In this study we demonstrated that the composition of interstitial inflammatory infiltrate is heterogeneous. This reflect the fact that allograft rejection can be mediated by a variety of immune mechanisms, includlnq Tlymphocytes and antibody, either directly or through antibody dependent cell mediated cytotoxicity and natural killer ceils. We demonstrated T- lymphocytes as the principle effector cells during acute rejection. Moreover, both T helper/inducer cells and T cytotoxic/suppressor cells can mediate allograft rejection. T helper cells have the main role as it represent the largest percentage in the interstitial inflammatory infiltrate. Also, T helper cells can mediate graft destruction via different immune mechanisms, mainly delayed-type hypersensitivity reactions via activation of macrophages. Also activate T cytotoxic cells that mediate graft damage via direct or indirect contact with graft cells and activate B-cells that mediate antibody- mediated immune reactions. While cytotoxic T- cells have the strongest or the severest effects, as its percentage in the infiltrate was increased directly with increasing of the grade of acute rejection (ie, the highest percentage in type III rejection). -133- Summary & Conclusion Other inflammatory cells were also detected in the interstitial inflammatory infiltrate, but present as a lesser percentage, as macrophages, natural killer and a-celts. These findings indicate that T- lymphocytes (mainly T helper cells) have the major role in the process of acute rejection but also the other inflammatory cells share in this process but to a lesser extent. In this study, we did not found that immunohistochemical analysis of interstitial inflammatory infiltrate have a predictive value on graft survival. In conclusion, immunohistochemical analysis of the interstitial inflammatory infiltrate gives a good idea about the events that occur inside the renal allograft during acute rejection and the immune mechanisms that are responsible for this, but it has no prognostic impact on graft survival. While, the new revised Banff (97) classification is the most predictive for graft survival. Among the histopathological criteria that diagnose acute rejection, vasculitis is the only predictive parameter for poor graft survival. Other variables are detected to have prognostic value on graft survival as number of both graft biopsies and acute rejection episodes, and pattern of the interstitial inflammatory infiltrate. As the increased number of graft biopsies, number of acute rejection episodes and the diffuse pattern of the interstitial infiltrate are associated with poor graft survival. |