INVESTIGADORES
CHULUYAN Hector Eduardo
congresos y reuniones científicas
Título:
Gene Expression Profiling in Kidney Transplant Correlation with DGF
Autor/es:
DIEGO GUERRIERI, LUIS RE, JORGELINA PETRONI, EDUARDO CHULUYAN, INCARDONA CLAUDIO, CASADEI H. DOMINGO
Lugar:
Philadelphia
Reunión:
Congreso; American Transplant Congress; 2011
Resumen:
[607] Gene Expression Profiling in Kidney Transplant Correlation with DGF.Diego
Guerrieri, Luis Re, Jorgelina Petroni, Eduardo Chuluyan, Incardona
Claudio, Casadei H. Domingo. Farmacología, Facultad de Medicina, UBA,
Argentina; Instituto de Nefrología Buenos Aires, Argentina; GADOR S.A.,
Buenos Aires, ArgentinaIntroduction:Ischemia
reperfusion injury (IRI) is a coordinated process leading to delayed
graft function (DGF) and reduced long-term graft survival of the
transplanted organ. Despite recent advances in organ procurement
management, DGF remains an important problem after kidney
transplantation. Different studies have related various clinical factors
to DGF, such as donor age, recipient age, cold ischemia time (CIT) and
initial immunosuppressive regimens.Objective and methods:The
aim of the present study was to determine if the development of DGF was
associated with a specific pattern of gene expression in deceased donor
kidney transplantation and, if it was the case, to explore the presence
of correlations b/w some transplant characteristics (CIT, donor &
recipient age) and the profile that was found. The study included 16
recipients of deceased renal grafts (11 males, 5 females): 12 of them
developed DGF and 4 patients show normal graft function(Table 1). A
pathway-specific cDNA microarray was used for gene expression profiling
and results were correlated with protocol biopsies 7 day
post-transplant.
Group 1 (DGF, n=12)
Group 2(no DGF, n=4)
Donor Age
56,5±4.2
53.3±2.2
Recipient Age
53.4±10.5
40.5±10.2
HLA MM(A, B, DR)
3.3±1.3
3.3±1.5
CIT
24±6
21±4Results:From
a total of 84 genes analyzed, 50 genes were up-regulated while only 1
gene was down-regulated in subjects with DGF compared with no DGF
(p=0.01). Table 2 shows the most relevant genes fold changes observed
based on DGF occurence.
Mediators
Fold of Change
Up-regulated
IL-1R1
4.9
IL-10
4.8
IFNA1
4.4
IL-1F7
4.3
CCR3
4.08
TLR8
3.5
IL-6
3
HMOX-1
2.9
TNF-α
2.7
Down-regulated
TGF-β1
3.3Although,
a pro-inflammatory profile was up-regulated in DGF patients compared
with no DGF, none of the transplant characteristics (CIT, donor &
recipient age) were correlated with this gene array profile.Conclusions:A
systematic biological assessment of these molecular changes suggests
that the inflammatory process driven by IRI is largely responsible for
DGF occurrence. DGF was associated in our study with an up-regulation of
certain pro-inflammatory genes and a down-regulation of some
anti-inflammatory mediators.