EXPRESSION OF IMMUNE ACTIVATION GENES IN BIOPSIES AFTER CARDIAC TRANSPLANTATION.
Shulzhenko N, Morgun A, Franco M, Almeida DR, Carvalho ACC,
Pacheco-Silva A, Diniz RVZ, Gerbase-DeLima M. Escola Paulista de Medicina,
UNIFESP, São Paulo, Brazil.
The objective of this study was to investigate the association
of intragraft expression of a series of immune activation genes with the
presence of histologically proven acute cardiac allograft rejection. We
have studied 46 endomyocardial biopsies collected at the time of regular
surveillance biopsies in 10 adult cardiac transplant recipients, during
the first six months after transplantation. The expression of IFN gama,
IL-8, CD40L, granzyme B, FasL, CD3, and beta-actin genes was studied using
the reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty two
biopsies showed at least grade 1B by the criteria of the ISHLT and were
considered as indicative of rejection. Fourteen grade 0 biopsies that had
been performed at least two weeks apart from the biopsy with rejection
were considered as without rejection. Ten biopsies did not match these
conditions and were excluded from the analysis. CD3 gene transcripts were
found in all the biopsies, indicating the invariable presence of T cells,
regardless of histologic rejection. The presence of mRNA of the other molecules
was associated with acute rejection. CD40L was present in 77% of the biopsies
with rejection and in 36% of the biopsies without rejection(p=0.016); IFN
gama, in 82 and 21% (p<0.001); IL-8, in 73 and 14% (p<0.001); granzyme
B, in 77 and 29% (p<0.01); FasL, in 86 and 43% (p<0.01), with and
without rejection, respectively. Thus, our results indicate that the detection
of gene expression of either immune regulating molecules, such as CD40L,
IFN gama, and IL-8, or immune effector molecules, such as FasL and granzyme
B, is highly associated with acute rejection and could represent a valuable
tool, in addition to histological evaluation, in the diagnosis of rejection.