Immunological monitoring in cardiac allograft vasculopathy

Abstract

Background The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV. Aim To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx. Methods We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells). Results The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p<0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (<1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis. Conclusions Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None.