22. Workshop für experimentelle und klinische Lebertransplantation ...

Transplantationsmedizin
Supplement I – 2011, S. 7
sessed by flow cytometry with the “BD
Cytometric Bead Array (CBA) Human
Th1/Th2/Th17 Cytokine Kit”. Student’s t-
test or Mann-Whitney-U-test, when appropriate,
was used for comparing continuous
variables.
Results: There were 36.8% females and
63.2% males with a mean age at LT of
47.1±11.6 years. A significantly increased
serum level of IFN-γ (1.4±0.6 vs
1±0.8pg/mL, p=0.007), TNF-α (1.1±0.4 vs
0.8±0.6pg/mL p=0.02), IL-10 (1.8±0.1 vs
1.3±0.1pg/mL, p=0.001), IL-6 (6.6±1.5 vs
4.1±1.5pg/mL, p=0.0001), IL-4 (1.3±0.6
vs 1±0.8pg/mL, p=0.03), IL-2 (1.7±0.8 vs
1.2±0.9pg/mL, p=0.01) were detected in
the subgroup with ITBL compared to controls.
IL-17 serum concentration and IL-
4/IFN-γ ratio did not differ between the 2
groups. IL-17 serum levels showed a positive
correlation with serum levels of IFN-γ
(r =0.43, p=0.007) and IL-2 (r =0.40,
p=0.01) in patients with ITBL. There was
a significantly higher ratio IL-4/IL-2
(p=0.04), IL-10/IFN-γ (p=0.01) and IL-
10/IL-2 (p=0.006) in the ITBL group compared
to controls. 37.2% of the patients
with ITBL had advanced fibrosis (F3-F4)
compared to 20.4% in the control group. In
the ITBL subgroup, patients with F3-F4
had significantly higher IL-6 levels compared
to patients with F0-F2 (p=0.02).
Conclusion: Inflammatory cytokines and
Th2-cell mediated immunity seem to play
a central role in the pathogenesis of ITBL.
Protocol liver biopsies for severe fibrosis
in ITBL patients should be performed in
patients with increased IL-6 serum levels.
Polymorphisms of Fractalkine
Receptor and Immunologic Risk
Factors for Anastomosis Stenosis
after Liver Transplantation
V. Cicinnati 1 , S. Iacob 1 , G. Wu 1 ,
A. Dechene 1 , M. Metzelder 2 , G. Gerken 1 ,
A. Paul 2 , S. Beckebaum 2
1
Klinik für Gastroenterologie und Hepatologie,
Uniklinikum Essen
2
Allgemein-, Viszeral- und Transplantationschirurgie,
Universitätsklinikum Essen
Introduction: Strictures at the site of the
bile duct anastomosis (AS) are major complications
following liver transplantation
(LT) and are thought to result mainly from
surgical technique and/or prolonged ischemia
times. For late AS, others than surgical
factors should be incriminated. Genetic
polymorphisms in chemokine receptors
which mediate leucocytes trafficking
to inflammatory sites, may be associated
with AS occurrence. Aim: To investigate
the role of immunologic and genetic risk
factors for development of AS after LT.
Methods: We prospectively genotyped 3
chemokine receptors (CCR2-V64I, CCR5-
D32, CX3CR1-V249I and T280M) in 137
LT recipients (44 with AS, 93 controls) by
PCR or PCR-restriction fragment length
polymorphism assay. Serum concentration
of chemokines CCL3 and CCL5, as ligands
of CCR5, and CX3CL1 as ligand of
CX3CR1 were measured by enzyme
linked immunosorbent assays.
Results: Median time to AS development
was 6.3 months (range 0.5-191 months).
The following risk factors with immunologic
involvement were identified for AS
occurrence: CX3CR1-249I/I (p=0.02),
acute liver failure as indication for LT
(p=0.03), ABO compatible, non-identical
LT (p=0.005). Independent variables associated
with AS were identified by multivariate
logistic regression analysis:
CX3CR1-249I homozygous allele
(p=0.03), acute liver failure as indication
for LT (p=0.01) and ABO compatible, nonidentical
LT (p=0.03). Serum concentrations
of CCL3, CCL5 and CX3CL1 were
similar between patients with AS and controls.
Conclusion: Proinflammatory and immunologic
factors predispose to AS development.
CX3CR1-249I homozygous allele,
as a promoter of liver fibrosis, was
identified as an independent risk factor for
AS after LT. CCR2 and CCR5 polymorphisms
had no influence in occurrence of
this type of biliary complication.