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DOI: 10.1055/s-0029-1191395
CTLA-4, FasL and granzyme B mRNA expression in sequential biopsies from heart allografts correlate with episodes of allograft rejection
Introduction: Investigation into the role of the immune system and the inflammatory cascade in acute rejection (AR) and cardiac allograft vasculopathy (CAV) has implicated costimulatory molecules such as CTLA-4 and markers of apoptosis such as granzyme b and Fas-L. The endomyocardial biopsy (EMB) has proven invaluable for the diagnosis of AR and provides information regarding the underlying biological processes following heart transplantation.
Methods: Here we analyzed 72 formalin-fixed and paraffin embedded sequential heart allograft biopsies from 22 patients by quantitative real-time reverse transcriptase-polymerase chain reaction for the mRNA expression of TNFα, IL6, TGFß, CTLA4 (CD152) granzyme B and FasL (CD178). mRNA expression levels were correlated to histological grade and time-point of rejection.
Results: A strong correlation was found between CTLA-4 gene expression and histologically proven rejection. Also increased mRNA levels were detected in biopsies with acute rejection for granzyme B and FasL respectively. In addition TGF-ß, which is involved in repair responses after tissue damage, showed higher expression patterns after episodes of acute rejection. Throughout the biopsies IL-6 levels were lower compared to other measured genes but also displayed a good correlation with allograft rejection.
Conclusion: Our results provide strong evidence that monitoring expression of CTLA-4, FasL and Granzyme B is an additive method in diagnosing and observing allograft rejection during human heart transplantation.