title: Does borderline kidney allograft rejection always require treatment?
abstract: BACKGROUND
  Borderline rejection (Bord-R) is a frequent diagnosis in renal transplantation, and there is increasing evidence that regulatory T lymphocytes are involved in its pathogenesis. Current histopathologic practice does not differentiate between graft-protecting and -damaging T lymphocytes, and patients with Bord-R routinely receive rejection treatment. We analyzed Treg-associated forkhead box P3 (Foxp3) gene expression in Bord-R and more severe forms of acute rejection episodes (ARE).
  
  
  METHODS
  Foxp3 transcripts were measured in 520 serial peripheral blood samples from 177 kidney graft recipients obtained during the first 20 days posttransplantation.
  
  
  RESULTS
  The highest Foxp3 transcripts were observed in patients with Bord-R or without rejection and the lowest in patients with ARE. Patients with Bord-R on posttransplant days 5 to 7 showed an increased Foxp3 transcript level of 156%, which increased to 302% by posttransplant days 14 to 16. In contrast, patients with ARE demonstrated significantly lower Foxp3 gene expression than that observed in Bord-R, nonrejectors, or acute tubular necrosis patients (P=0.001, P<0.001, and P=0.005, respectively, on days 11-13). Acute tubular necrosis patients demonstrated intermediately high Foxp3 gene expression.
  
  
  CONCLUSIONS
  Our data indicate that increased Treg activity in peripheral blood is a frequent feature of Bord-R. This finding questions the appropriateness of rejection treatment in all patients with the histopathologic diagnosis "Bord-R".
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Németh
authors.forename: Jörg
authors.initials: J
authors.lastname: Ovens
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
authors.forename: Luis E
authors.initials: LE
authors.lastname: Becker
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Gross
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Markus
authors.initials: M
authors.lastname: Mieth
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Robert M
authors.initials: RM
authors.lastname: Langer
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
mesh_terms: D000328:Adult; D017931:DNA Primers; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000235:genetics; D006084:Graft Rejection / Q000188:drug therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009876:Operon / Q000235:genetics; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000473:pathology
chemical_list: D017931:DNA Primers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents