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Expression of cytotoxic mediators (perforin, granzyme B, FAS, and FAS-l) in renal allograft biopsies

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Author(s):
Leitao, Therezinha Gauri ; Becker, Luid Eduardo ; de Oliveira, Ivone Braga ; de Siqueira, Flavia Ramos ; Regina, Maria ; Araujo, Teixeira ; Romao Junior, Joao Egidio ; Abensur, Hugo ; Noronha, Irene de Lourdes
Total Authors: 9
Document type: Journal article
Source: Einstein (São Paulo); v. 4, n. 4, p. 7-pg., 2006-10-01.
Abstract

Objectives: To analyze the in situ expression of perforin, granzyme B, FAS-L and FAS in renal allograft biopsies by means of immunohistochemistry and correlate these findings with the degree of histologic rejection and allograft outcome. Methods: Ninety-six allograft biopsies were divided into three groups: acute rejection (n = 56), chronic rejection (n = 31), and cases with stable renal function (no rejection; n = 9). The expression of perforin, granzyme B, FAS-L, and FAS was evaluated by immunohistochemistry. Results: A significantly higher expression of perforin and granzyme B was observed in acute rejection biopsies (4.83 +/- 0.65 and 30.05 +/- 7.93 cells/mm(2)) compared to chronic rejection biopsies (0.71 +/- 0.13 and 11.4 +/- 3.84 cells/mm2; p < 0.001, and p < 0.05, respectively), but this was not the case for FAS-L (24.44 +/- 5.56 in acute rejection versus 18.87 +/- 6.83 in chronic rejection). Perforin, granzyme B, and FAS-L expression was significantly higher in the acute rejection group compared to the no rejection and control groups. FAS expression was similar in all groups. A modest correlation between perforin expression and the severity of AR was observed (r = 0.28, p = 0.05). Perforin was the most reliable marker for acute rejection diagnosis, with 80% sensitivity and 84.3% specificity. Conclusion: The in situ expression of perforin, granzyme B, and FAS-L in AR reflects the presence of an active cytotoxic process. Additional allograft biopsies are necessary in order to evaluate the usefulness of these markers for allograft rejection monitoring. (AU)