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33
october 7-9, 2012 • NEW ORLEANS, LA
P5
PLASMOCYTOID DENDRITIC CELLS AS BIOMARKERS
FOR ACUTE CELLULAR REJECTION AFTER HEART
TRANSPLANTATION
Markus J Barten, Maja T Dieterlen, Attila Tarnok, Stefan Dhein,
Friedrich W Mohr, Hartmuth B Bittner Heart Center Leipzig
Background:
Over the last years studies in liver transplanted
recipients have shown that plasmocytoid dendritic cells
(pDCs) have the potential to be biomarkers for tolerance.
Thus, we investigated the influence of tacrolimus (TAC)-
based in comparison with cyclosporine A (CsA)-based
immunosuppressive therapies on DCs in correlation with the
incidence of rejection in heart transplant recipients (HTxR).
Methods:
All HTxR received either CsA or TAC in combination
of a daily fixed dose of mycophenolic acid (MPA) and steroids.
Blood from all HTxR was taken to analyse for blood CsA or
TAC concentration before drug administration. FACS analysis
was performed to assess myeloid (m) and plasmocytoid DCs in
peripheral blood. Endomyocardial biopsy was done to classify
the histologic grade of rejection by a pathologist blinded to
drug therapy. A moderate rejection grade (ISHLT 2004) was
considered to be clinically significant.
Results:
Mean time
after HTx was 35.9±11.8months for the CsA-group and 45.1±
15.1months for the TAC-group. Overall HTxR with rejection had
significant (p<0.05) lower pDC values (55.1±16.2%) than HTxR
without rejection (63.6±10.5%). The influences of TAC and CsA
on DCs were significantly (p<0.05) different: 1) mDCs were less
in the TAC-group (45.2±10.7%) vs. CsA-group (58.0±19.1%),
2) pDCs were higher in the TAC-group (67.5±8.4%) vs. CsA
group (53.9±13.0%).
Conclusions:
Our results showed for the
first time that low pDC values in peripheral blood identify HTxR
at risk for rejection. Furthermore, we found different affects of
immunosuppressive drugs on pDCs. Future studies in a larger
cohort of HTxR are necessary to confirm our findings.
P6
HIGHER AND EARLIER INCIDENCE OF CARDIAC
ALLOGRAFT VASCULOPATHY IS ASSOCIATED WITH NON-
HLA ANTIBODIES
Markus J Barten, Maja T Dieterlen, Sandy von Salisch, Stefan
Dhein, Friedrich W Mohr, Hartmuth B Bittner
Heart Center Leipzig
Objective:
Cardiac allograft vasculopathy (CAV) after heart
transplantation (HTx) is a major therapeutic challenge, occuring
in more than 50% of HTx recipients in the first years after
transplantation. Antibodies against human leukocyte antigens
(HLA) and non-HLA antigens like major histocompatibility
complex class I-related chain A (MICA), angiotensin type 1
receptor (AT1R) or endothelin receptor A (ETAR) increasingly
gain importance as modulators of allograft function and,
therefore, recipient survival.Methods: Sera of 116 HTx
recipients were screened post-transplantation by Luminex-
technology for HLA and MICA antibodies and their donor
specificities. Non-HLA antibodies against AT1R and ETAR
were analysed by ELISA. For statistical analysis gender, age,
status of CAV and CMV seropositivity were documented.
Results: Gender, age or CMV infection had no influence on
the incidence of CAV. In general, HTx recipients developed
antibodies against HLA class I or class II to a lower extend
than against non-HLA antigens. CAV appeared more frequently
in recipients with non-HLA antibodies (38.3% AT1R; 44.1%
ETAR; 13.0% MICA) than in recipients with HLA antibodies
(8.7% HLA class I; 8.7% HLA class II). Furthermore, recipients
with non-HLA antibodies developed CAV earlier (73.7±47.4mo)
than recipients without non-HLA antibodies (85.5±50.6mo).
Donor specific antibodies against HLA-B46, -B76, -DQ7,
-DQ8, MICA19 were identified as risk factor for CAV in this
content. Conclusions: Both HLA and non-HLA antibodies had
an influence on CAV after HTx. Especially, non-HLA antibodies
POSTER ABSTRACTS