Allograft Inflammatory Factor-1 Expression Correlates With Cardiac Rejection and Development of Cardiac Allograft Vasculopathy

Abstract

Background— Standard morphological features of endomyocardial biopsy specimens do not necessarily correlate with the efficacy of immunotherapy or development of cardiac allograft vasculopathy (CAV). We hypothesized that expression of allograft inflammatory factor-1 (AIF-1), a cytokine-inducible, calcium-binding protein associated with vascular smooth muscle cell proliferation, would be associated with allograft rejection and development of CAV. Methods and Results— A total of 157 endomyocardial biopsy specimens from 26 patients with heart transplants were examined for expression of AIF-1 mRNA by semiquantitative reverse transcription–polymerase chain reaction. A significant relation was found between the International Society for Heart and Lung Transplantation rejection grade and expression of AIF-1 ( P <0.001). The calculated odds ratio indicates that a biopsy has 2.5 times the chance of AIF-1 expression per grade of rejection. The relative concentrations of AIF-1 and GAPDH mRNA were calculated and the resulting ratios indicated that the amount of AIF-1 mRNA expression is relative to the rejection grade ( P <0.02). In grade 1 biopsy specimens, AIF-1 was localized to infiltrating immune cells. In grade 3 biopsy specimens, AIF-1 was observed in immune cells and myocytes. AIF-1 is expressed in vascular and immune cells in coronary arteries with CAV, and persistent expression of AIF-1 in the allograft correlates with development of CAV ( P <0.002). Conclusions— Expression of AIF-1 in cardiac allografts correlates with rejection, and the amount of AIF-1 expressed correlates with the severity of rejection. AIF-1 is expressed in coronary arteries with CAV, and persistent expression of AIF-1 in the cardiac allograft is associated with development of CAV.

Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

“…The allograft inflammatory factor 1 ( Aif1 ), was cloned from chronically rejecting rat cardiac allografts [32] and it was also found in transplanted human hearts [33]. Persistent expression of AIF-1 is associated with the development of a cardiac allograft vasculopathy [34]. The expression of AIF-1 is mostly limited to the monocyte/macrophage lineage, and can be augmented by interferon (IFN)-γ.…”

Warm Ischemia-induced Alterations in Oxidative and Inflammatory Proteins in Hepatic Kupffer Cells in Rats

“…Increased numbers of AIF-1-immunoreactive macrophages have been observed in brain infarctions and injury, gliomas, rat uveitis, and inflammatory lesions of a rat model of autoimmune disease (38). Furthermore AIF-1 transcript levels have been shown to be increased in rejection of the heart and kidney (40,41).…”

Biomarkers of acute rejection following cardiac transplantation

“…Serum CXCL-9 and -10 levels measured before, during and after rejection No significant change in serum concentrations of CXCL-9 or CXCL-10 during cardiac rejection, despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection AIF-1 AIF-1 is an IFN-γ-inducible calcium binding protein that has been shown in several small studies to demonstrate positive immunostaining on endomyocardial biopsies with evidence of rejection [120][121][122] No studies assessed if there was release of AIF-1 into the circulation to allow potential for its use as a serum biomarker Antibodies directed at angiotensin II type 1 receptor antibodies (AT1R) [109,110], endothelin-1 type A receptors [110], collagen-V [109] and K-α1-tubulin [109] have also been associated with AMR in small studies.…”