Intragraft mRNA cytotoxic molecule expression in renal allograft recipients.
The gene expression of the cytotoxic T-cell molecules perforin, granzyme B and Fas ligand are associated with acute rejection in renal allograft recipients. Several immune mechanisms are linked to severe systemic inflammation in brain-dead organ donors. We examined the mRNA expression of these T-cell activation biomarkers in donor kidney biopsies to evaluate if they could separate living from deceased donors and primary graft function from delayed graft function or acute rejection in the early post transplantation period. We obtained 139 cadaveric and 19 living donor kidney core biopsies post reperfusion and 78 renal allograft biopsies taken because of graft dysfunction. RNA was isolated from tissue samples and mRNA encoding perforin, granzyme B or Fas ligand and a constitutively expressed cyclophilin B, a reference gene, was measured with the use of real-time quantitative polymerase chain reaction assay, and the levels of expression was correlated with allograft status. We did not find statistically significant differences in gene expression of perforin, granzyme B or Fas ligand among deceased and living donor kidneys and the mRNA expression of these cytotoxic molecules in donor kidney biopsies did not distinguish primary allograft function or early acute rejection. Significant differences were found between acute rejection (n=17) and zero-hour samples and acute rejection and non-rejection (n=41) samples for all 3 measured transcripts. No significant difference was found between acute borderline rejection (n=16) and non-rejection samples. In conclusion, effector molecules secreted by cytotoxic T lymphocytes were not activated in deceased donor kidneys and the genes did not classify the post-transplant course.
Carstens
J
J
Department of Renal Medicine, Skejby Hospital, Aarhus University Hospital, Aarhus, Denmark. drjc@dadlnet.dk
Ozbay
A
A
Tørring
C
C
Hansen
H E
HE
D001706:Biopsy; D002102:Cadaver; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D051799:Delayed Graft Function / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D053804:Granzymes / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D054353:Perforin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D019737:Transplants
D053222:Fas Ligand Protein; D012333:RNA, Messenger; D054353:Perforin; D053804:Granzymes