Plasma Immunoglobulin Levels Prior to Cardiac Transplantation are Associated with Post-Transplantation Survival

Purpose
It is difficult to predict which patients will have a long term survival after heart transplantation (HTx). Cardiac allograft vasculopathy (CAV) and antibody mediated rejection are long-term morbidities after HTx limiting survival. Both are caused by an immune response against the donor heart. Interestingly, already prior to HTx increased plasma levels of immunoglobulins have been found in end-stage heart failure patients. We hypothesized that an activated adaptive immune system pre-HTx can influence graft survival. Therefore, the objective of this study was to determine whether circulating immunoglobulins pre-HTx are associated with post-HTx survival.

Methods
Epicardial tissue was collected from 61 HTx recipients at autopsy. In addition, of 36 of these patients plasma samples pre-HTx until 6 months post-HTx were collected. Immunoglobulin levels were measured in plasma samples and tissue lysates and correlated to survival-time post-HTx and histological CAV phenotype.

Results
High pre-HTx plasma levels of IgG1 and IgG2 were associated with a shorter survival-time post-HTx. Patients with high plasma immunoglobulin levels pre-HTx also revealed high plasma levels in the first 6 months after HTx, whereas patients with low pre-HTx levels remained low. Similarly, in the cardiac tissue immunoglobulin deposition was significantly increased in patients with a survival of less than 3 years compared to patients with long term survival. Both in pre-HTx plasma and post-HTx in the donor heart, IgG1 and IgG2 levels were significantly increased in patients with an inflammatory CAV type.

Conclusion
High pre-HTx immunoglobulin levels are associated with a shorter overall survival, thereby suggesting that an activated adaptive immune system before transplantation might have an adverse effect on graft survival.