Prognostic Role of MMP2, MMP9, and IL-1β Markers in Cardiac Allograft Rejection After Transplantation

Abstract

Cardiac allograft rejection remains a major cause of graft dysfunction post-transplant. While histology is the current diagnostic standard, it may miss early immune and inflammatory events. This study evaluated the immunohistochemical expression of matrix metalloproteinases 2 (MMP2), 9 (MMP9), and interleukin-1 beta (IL-1β) in cardiac transplant patients, correlating their expression with acute cellular rejection (ACR), antibody-mediated rejection (AMR), inflammation, vasculitis, the Quilty effect, and immune markers. Fifty-nine endomyocardial biopsy specimens were retrospectively analyzed. Immunohistochemical staining for MMP2, MMP9, and IL-1β was assessed based on nuclear, cytoplasmic, and membranous expression. Correlations were evaluated using Fisher’s exact test and odds ratios (ORs) with 95% confidence intervals (CIs). IL-1β nuclear expression showed strong associations with ACR (p = 0.0001), inflammation, vasculitis, and immune/endothelial markers (all p < 0.003). Nuclear MMP9 expression correlated with ACR and immune cell markers and was borderline significant for AMR (p ≈ 0.05). Cytoplasmic MMP2 (>50%) was significantly associated with AMR (OR = 7.47, p = 0.0002). No marker correlated with the Quilty effect. The immunohistochemical profiles of IL-1β and MMP9 support their involvement in immune-mediated injury in cardiac allograft rejection, with IL-1β emerging as a sensitive marker of early inflammation. MMP2 appears to be more relevant to humoral rejection processes. These findings suggest that selected tissue biomarkers may enhance diagnostic precision and support early detection of graft injury when integrated with conventional histology.