Clinical application of molecular biology: a study of allograft rejection with polymerase chain reaction.
This article explores the clinical usefulness of reverse transcriptase-polymerase chain reaction in organ graft recipients. In this study, reverse transcriptase-polymerase chain reaction 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 human renal allograft biopsies. The biopsies (n = 127) were classified using the Banff criteria, and intrarenal gene expression was correlated with the histologic 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 is a correlate of chronic rejection. In addition to demonstrating differential and highly selective intragraft gene expression during rejection, these data suggest that therapeutic strategies directed at the molecular correlates of rejection might refine existing antirejection strategies.
Suthanthiran
M
M
Division of Nephrology, New York Hospital-Cornell Medical Center, New York, USA.
D016207:Cytokines / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D053804:Granzymes; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D054353:Perforin; D012194:RNA-Directed DNA Polymerase; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases