Occurrence of HLA- and non-HLA antibodies after heart transplantation are associated with cardiac allograft vasculopathy

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Original research

Occurrence of HLA- and non-HLA antibodies after heart transplantation are associated with cardiac allograft vasculopathy

Maja-Theresa Dieterlen1Jens Garbade1Robert Riede1Stefan Dhein1Friedrich W. Mohr1Hartmuth B. Bittner2Markus J. Barten1*

1 University of Leipzig, Department of Cardiac Surgery, Heart Center, 04289 Leipzig, Germany
2 Florida Hospital Orlando, Department Cardiothoracic Transplantation and Advanced Cardiac Surgery, Orlando, Florida, USA

* Corresponding author:
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Cardiac allograft vasculopathy (CAV) accounts for major morbidity and mortality late in the heart transplant (HTx) history. The role of antibodies (Abs) directed against human leukocyte antigens (HLA) and non-HLA antigens in the pathogenesis of CAV are still under investigation.

Materials and methods

Sera of 116 long-term HTx recipients with CAV (n=46) and without CAV (n=70) were analysed by (1) Luminex for Abs against both HLA classes and major histocompatibility complex class I-related chain A (MICA), and by (2) ELISA for Abs against angiotensin-type-1-receptor (AT1R) or endothelin-receptor-A (ETAR). Cellular rejection by endomyocardial biopsies and immunosuppressive drug therapy were analysed, too.


HTx recipients developed higher levels of non-HLA-Abs than of Abs against HLA. CAV appeared more frequently in recipients with non-HLA-Abs (38.3% AT1R; 44.1% ETAR; 13.0% MICA) than in recipients with HLA-Abs (8.7% HLA class I; 8.7% HLA class II). Recipients with non-HLA-Abs developed CAV earlier (73.7±47.4months) than recipients without Abs (85.5±50.6months).


Occurrence of HLA-Abs and non-HLA-Abs contribute to CAV after HTx. Non-HLA-Abs were connected to an earlier and higher incidence of CAV. Recipients with subclinical cellular rejections and AT1R-Abs and ETAR-Abs as well as recipients with certain donor specific-Abs again HLA and MICA specifities are at risk to develop CAV.


Maja-Theresa Dieterlen, Jens Garbade, Robert Riede, Stefan Dhein, Friedrich W. Mohr, Hartmuth B. Bittner, Markus J. Barten. Occurrence of HLA- and non-HLA antibodies after heart transplantation are associated with cardiac allograft vasculopathy; Cardiometry; No.4; May 2014; p.71-85; DOI:10.12710/cardiometry.2014.4.7185 Available from: http://www.cardiometry.net/no4-may-2014/cardiac-allograft-vasculopathy


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