title: The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation.
abstract: BACKGROUND
  An important limitation to the success of lung transplantation is the development of bronchiolitis obliterans syndrome (BOS). It has been hypothesized that regulatory T lymphocytes (Tregs) are related to the risk of BOS. We aim to evaluate whether the number of forkhead box P3 (FoxP3+) cells/mm(2) in lung allograft biopsies is a predictor of long-term outcome.
  
  
  METHODS
  A total of 58 consecutive lung transplant patients were included in the study. For 233 routine surveillance biopsy samples, the numbers of FoxP3+ cells/mm(2) were assessed by immunohistochemical staining with antibodies against FoxP3. BOS scores were calculated for the first five yr after transplantation.
  
  
  RESULTS
  We determined that acute rejection was related to the time elapsed from transplantation to BOS with hazard ratios of 3.18 (p = 0.02) and 3.73 (p = 0.04) when comparing the levels of acute rejection grade 1 and grade 2/3, respectively, to no rejection. According to a Cox regression analysis, the number of FoxP3+ cells/mm(2) was not predictive of time to BOS.
  
  
  CONCLUSIONS
  Our data indicate that the number of FoxP3+ cells in the lung allograft did not correlate with BOS-free survival time. Previous studies have been contradictory and included different time points. Our findings emphasize the importance of including a time factor.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Dorrit
authors.initials: D
authors.lastname: Krustrup
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.forename: Torben
authors.initials: T
authors.lastname: Martinussen
authors.forename: Hans Henrik L
authors.initials: HH
authors.lastname: Schultz
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts / Q000276:immunology / Q000473:pathology; D015415:Biomarkers; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: acute rejection; bronchiolitis obliterans syndrome; forkhead box P3; histopathology; lung transplantation; regulatory T cells