Background: The first year after cardiac transplantation is critical for transplant survival and long-term outcome. Identification of suitable biomarkers for detection of rejection processes is still of great importance. In our study, we assessed a biomarker panel profile within the first twelve months after transplantation.

Methods: Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNγ, the chemokines IP10 and MIG, subsets of dendritic cells as well as antibodies against human leukocyte antigens (HLA) and major histocompatibility complex class I-related chain A (MICA)-antigens were analyzed at five different time points within the first year using flow cytometry and Luminex xMAP technology.

Results: Levels for CD25, CD95, IP10, MIG and myeloid dendritic cells did not change during the first year, whereas expression of IL-2, IFNγ and plasmacytoid dendritic cells significantly increased (p<0.01 for each). Anti-HLA antibodies decreased continuously, while anti-MICA antibodies showed minor increase within the first year. We could not detect differences between recipients with mild acute cellular rejection and recipients without ACR regarding cellular parameters and cytokines. An association between percentage of plasmacytoid dendritic cells and anti-MICA antibody positivity was proven. Furthermore, analysis revealed that plasmacytoid dendritic cells, IFNγ-producing T cells and IP10-concentration were associated in a stronger way with age and gender of HTx recipients than with antibodies against HLA or MICA.

Conclusions: We recommend quantification of CD25, IL-2, IFNγ, plasmacytoid dendritic cells and monitoring of anti-HLA and anti-MICA antibodies after cardiac transplantation to display patient-specific changes of immunological status and therefore, to improve identification of patients with higher risk for rejection. According to our result, we specified further recommendations for clinical validation process for biomarkers.

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