Research Article
Assessment of Immunological Biomarkers in the First Year
after Heart Transplantation
Maja-Theresa Dieterlen,
1
Katja John,
1
Hartmuth B. Bittner,
2
Meinhard Mende,
3
Attila Tarnok,
4
Friedrich W. Mohr,
1
and Markus J. Barten
5
1
Clinic for Cardiac Surgery, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany
2
Division of Toracic Transplantation, Florida Hospital Orlando, Orlando, FL 32803, USA
3
Clinical Trial Centre Leipzig, University of Leipzig, 04103 Leipzig, Germany
4
Department of Pediatric Cardiology, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany
5
Department of Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany
Correspondence should be addressed to Maja-Teresa Dieterlen; mdieterlen@web.de
Received 18 August 2015; Revised 10 September 2015; Accepted 10 September 2015
Academic Editor: Claudio Letizia
Copyright © 2015 Maja-Teresa Dieterlen et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Background. Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful
tool to increase the efcacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers
following transplantation are not investigated. Terefore, we assessed frequently used immunological biomarkers of the circulating
blood in the frst year following heart transplantation (HTx). Methods. Activation markers CD25 and CD95, intracellular cytokines
IL-2 and IFN, 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 diferent time points
using fow cytometry and Luminex xMAP technology. Results. Expression of IL-2, IFN, and plasmacytoid dendritic cells (pDCs)
signifcantly increased ( < 0.01) during the frst year. Anti-HLA antibodies decreased continuously, while anti-MICA antibodies
showed minor increase within the frst year. An association between percentage of pDCs and anti-MICA antibody positivity was
proven. pDCs, IFN-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 frst year afer HTx. Tese changes should be considered for interpretation of biomarkers afer
transplantation.
1. Introduction
Predictive biomarkers play a major role in identifying
transplant rejection following solid organ transplantation.
Especially afer heart transplantation (HTx), the frst year
is critical for transplant survival and long-term outcome.
Te post-HTx follow-up care includes the pharmacokinetic
control of immunosuppressive drug blood levels as well
as histopathological analyses of endomyocardial biopsies
(EMBs) in periodical intervals. However, this strategy does
not avoid over- or underimmunosuppression which on their
part ofen leads to severe infection or allograf rejection,
respectively.
Diferent patient-specifc responses of the immune sys-
tem seem to be the reason for the variable efcacy of
immunosuppressive drug therapies. Te reason for the vari-
able efcacy of immunosuppressive drug therapies is due to
the diferent, patient-specifc response of the immune system.
For an enhanced estimation of the efectiveness of immuno-
suppressive drug therapies, pharmacodynamic monitoring
becomes more and more important. Te clinical research in
the last decade focused on the identifcation of biomarkers
Hindawi Publishing Corporation
Disease Markers
Volume 2015, Article ID 678061, 8 pages
http://dx.doi.org/10.1155/2015/678061