title: Intrahepatic detection of FOXP3 gene expression after liver transplantation using minimally invasive aspiration biopsy.
abstract: Intragraft accumulation of Forkhead box P3 (FOXP3)-positive regulatory T cells (Treg) is associated with local suppression of alloresponses in transplantation models. In the current study, the utility of the minimally invasive fine needle aspiration biopsy for the intragraft detection of FOXP3 and interferon (IFN)-gamma mRNA expression was investigated in clinical liver transplantation (LTx). Intragraft FOXP3 increased within the first year after LTx, but not in blood. Elevated FOXP3, but not IFN-gamma expression, in the liver was observed after hepatitis C virus (HCV) reinfection and after a previous episode of acute rejection. These data show the feasibility of aspiration biopsy for intragraft monitoring of gene expression. Intrahepatic FOXP3 levels are associated with HCV reinfection, a history of acute rejection, and increased within the first year after LTx. Differences in gene expression between the graft and blood underline the importance of local immune monitoring.
authors.affiliation: Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Demirkiran
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Alice
authors.initials: A
authors.lastname: Kok
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
mesh_terms: D000328:Adult; D044963:Biopsy, Fine-Needle / Q000379:methods*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000175:diagnosis / Q000378:metabolism; D006526:Hepatitis C / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D016031:Liver Transplantation / Q000009:adverse effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D007371:Interferon-gamma