Cardiologia Clínica e Experimental
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AIF-1 Gene Expression and Polymorphism in Association with Cardiac Allograft Rejection

D.O. McDaniel, L. K. Piazza, Andrea Barker, H. Robertson, C. K. Moore, X. Zhou, P. Redmond, Y. Jackson and G. Aru

Long- term clinical outcomes after cardiac transplantation still remains a challenge because of rejection episodes and the development of coronary vasculopathy. Rejection episode (RE) is a complex immunologic response, associated with the inflammatory signaling network. Allograft inflammatory factor-1 (AIF-1) has an important role in inflammatory process associated with transplantation. The goal was to demonstrate an association between the AIF-1 gene expression and genotype variation with RE. Peripheral blood and endomyocardial specimens were tested by semi-quantitative RT-PCR and immunohistochemistry (IHC) stains for identification of AIF-1 and IL-18 and were analyzed against clinical ISHLT grades for rejection. Sequence-specific primers for AIF-1 gene polymorphism were used to determine the C or the T allele variation in association with RE. The prevalence of CT heterozygous alleles were found significantly higher in patients who were presented with (0) RE during the first 6 months after transplantation as compared with CC alleles. The correlation of having CT alleles versus CC were inversely distributed with the increase in the number of RE. The isoform 2 expression was almost 2-fold higher than isoform 1 or isoform 3 in specimens with grade 3A RE versus specimens with grade 0-1 RE (p<0.001). The AIF-1 and the IL-18 were present in CMCs and in most of the MNCs in the specimens with grade 3A RE. The AIF-1 mRNA transcript expression was increased 5-fold in the biopsy specimens and it was1.7-fold higher than in peripheral blood monocytes in grade 3A RE. The IL-18 expression was increased 4.2-fold in biopsy specimens presented with 3A versus grade 0 (N) RE. Individuals with AIF-1 CC alleles are at a greater risk of developing the early rejection episodes. AIF-1 could serve as a suitable biomarker to monitor cardiac allograft RE through a less invasive procedure.