Expression of allograft inflammatory factor-1 (AIF-1) in acute cellular rejection of cardiac allografts

Abstract

To date, there are no good biomarkers for diagnosing and predicting the progression of cardiac allograft rejection. Previous studies have shown a correlation of allograft inflammatory factor-1 (AIF-1) to human cardiac allograft rejection; however these studies were limited in sample size and did not address whether AIF-1 could be used as a biomarker in diagnosing and predicting the progression of cardiac allograft rejection. Using immunohistochemistry, AIF-1 expression was determined in cardiomyocytes (CMCs), mononuclear cells (MNCs) and Quilty lesions in 192 allograft endomyocardial biopsies and 37 heart specimens from nontransplant patients with diverse heart diseases. AIF-1 was found in both cardiac allografts and hearts with other cardiac diseases. In cardiac allografts, expression levels of AIF-1 in both CMCs and MNCs directly correlated with the severity of cardiac cellular rejection. AIF-1 expression was also elevated in Quilty B lesions, but not in Quilty A lesions. The rejection grade in subsequent biopsies increased in biopsies that had low-grade rejection with high CMC AIF-1 scores or Quilty B lesions. AIF-1 was expressed in both CMCs and MNCs in hearts with various adverse conditions including but not limited to heart transplantation. In cardiac transplantation, AIF-1 was associated with the severity of cardiac allograft rejection and Quilty B lesions, which could predict subsequent increases in rejection grade. Thus, AIF-1 shows promise that it can be a potential biomarker for cardiac allograft rejection.