Molecular analyses of human renal allografts: differential intragraft gene expression during rejection.
Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify intrarenal expression of cytotoxic attack molecules (granzyme B and perforin) and immunoregulatory cytokines (IL-2, IL-4, IL-10, IFN-gamma, and TGF-beta 1) in 127 human renal allograft biopsies. The biopsies were classified using the Banff criteria, and intrarenal gene expression was correlated with the histological diagnosis. Molecular analyses revealed that intragraft display of mRNA encoding granzyme B, IL-10 or IL-2 is a correlate of acute rejection, and intrarenal expression of TGF beta 1 mRNA, of chronic rejection. These data, in addition to demonstrating differential and highly selective intragraft gene expression during rejection, suggest that therapeutic strategies directed at the molecular correlates of rejection might refine existing anti-rejection strategies.
Suthanthiran
M
M
Department of Medicine, Department of Transplantation Medicine and Extracorporeal Therapy, New York, New York, USA.
D001706:Biopsy; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics*; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000201:enzymology / Q000601:surgery; D016030:Kidney Transplantation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics; D016376:Oligonucleotides, Antisense; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014184:Transplantation, Homologous
D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D054353:Perforin; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases