Assessment of Immunological Biomarkers in the First Year after Heart Transplantation.
BACKGROUND
Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful tool to increase the efficacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers following transplantation are not investigated. Therefore, we assessed frequently used immunological biomarkers of the circulating blood in the first year following heart transplantation (HTx).


METHODS
Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNγ, chemokines IP10 and MIG, and 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 different time points using flow cytometry and Luminex xMAP technology.


RESULTS
Expression of IL-2, IFNγ, and plasmacytoid dendritic cells (pDCs) significantly increased (p < 0.01) during the first year. Anti-HLA antibodies decreased continuously, while anti-MICA antibodies showed minor increase within the first year. An association between percentage of pDCs and anti-MICA antibody positivity was proven. pDCs, 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 conclude that certain immunological biomarkers of the circulating blood change during the first year after HTx. These changes should be considered for interpretation of biomarkers after transplantation.
Clinic for Cardiac Surgery, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany.
Maja-Theresa
MT
Dieterlen
Clinic for Cardiac Surgery, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany.
Katja
K
John
Division of Thoracic Transplantation, Florida Hospital Orlando, Orlando, FL 32803, USA.
Hartmuth B
HB
Bittner
Clinical Trial Centre Leipzig, University of Leipzig, 04103 Leipzig, Germany.
Meinhard
M
Mende
Department of Pediatric Cardiology, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany.
Attila
A
Tarnok
Clinic for Cardiac Surgery, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany.
Friedrich W
FW
Mohr
Department of Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.
Markus J
MJ
Barten
D000328:Adult; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects*; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D018925:Chemokines; D015395:Histocompatibility Antigens Class I; D053645:Interleukin-2 Receptor alpha Subunit; C099187:MHC class I-related chain A; D019014:fas Receptor