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Interleukin 17 expression evaluation in kidney transplantation

Grant number: 10/04698-4
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2012
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alvaro Pacheco e Silva Filho
Grantee:Luciana Mello de Mello Barros Pires
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Chronic allograph nephropaty is the main cause of renal engraftment loss. Amongst the more important risk factors for this outcome it is distinguished acute rejection. Rejection of organs and tissues involves an interaction between tolerance mechanisms and the rejection promotional factors. While imunology factors are important for both, the rejection process is much more consequent of an inflammatory process. The linfocytes infiltrated and the resident epithelial cell produce some of pro-inflamatory citokines. Animal models of renal transplant rejection had been capable to identify in the graft a higher mRNA expression of interleukin-17 associated with presence of interleucina-17 protein, in infiltrated mononuclear cells, so early as in as the day after-transplant. The biological actions of interleucina-17 are characteristically pro-inflammatory. It increases the local production of quimioquinas as the IL-8, IL-6, monocyte chemo attractant protein-1 (MCP-1) and Gro±, thus promoting the recruitment of monocytes and neutrophils. The IL-17 also stimulates hematopoietic G-CSF and macrophages (GM-CSF) cytokines that will promote the myeloid line clonal expansion. IL-17 expression has been suggested to relate to acute rejection of renal transplant in previous studies analyzing Real Time PCR (RT-PCR) and immunohistochemistry. Experimental studies had demonstrated the presence of cytokines Th1 and Th2 in acute cellular rejection, had failed in demonstrating the correlation between the cytokines levels of expression and the severity of the rejection. Only one study in mice model of rejection showed a correlation between the level of expression of interleukine-17 and the level of rejection.The main objective of this study is to relate the expression of IL-17 with different types of renal graft acute rejection. As secondary objectives the IL-17 activity will be evaluated by the expression of Interleukine-6 and 8. CD20 will be used to evaluate the lymphocyte infiltration, and the evaluation of the complement cascade will be done by C3. Therefore this study will not only demonstrate the presence of the ILl-17 but more important will identify the activity of this interleukin. This will be a retrospective study with biopsy samples from patients who had received renal transplantation. The 140 biopsies were carried out by the medical assistant group, in the period between January of 2007 the June of 2009. This material will be divided in groups in agreement with the Banff criteria. By this study we expect to demonstrate a better agreement of the Interleukin 17 pattern and other inflammatory mediators during the renal graft acute rejection, which may be a future target for immunomodulation.