The role of immunological biomarkers in cardiac rejection

To summarize the promises and limitations of candidate noninvasive immunological biomarkers in cardiac rejection, with a special focus on the chemokine CXCL10, as a pretransplant predictive marker of early heart acute rejection. Potential issues for transfer from research to the clinic are addressed.

Early changes of immune biomolecules in peripheral blood, reflecting graft or heart recipient's immune status, are candidate biomarkers able to diagnose or predict cardiac rejection, ideally giving an opportunity to intervene before heart failure occurs. The support of robust analytical methodologies is necessary for the transition from biomarker discovery to clinical implementation.

Cardiac rejection represents the main problem after heart transplantation. Endomyocardial biopsy, although invasive and not risk free, is the gold-standard procedure for rejection monitoring. Noninvasive heart damage biomarkers manifest substantially after rejection occurrence. The goal is to detect graft injury at the earliest possible stage in disease initiation. Some biomolecules associated with the early immune response to cardiac allograft retain the power to be diagnostic and, even better, predictive of acute rejection, as in the case of pretransplant CXCL10 serum level. Multicenter studies for assay validation and standardization, integrated analysis of multiple biomarkers, and cost-effectiveness evaluation are mandatory efforts.