Does borderline kidney allograft rejection always require treatment?
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".
Németh
Dorottya
D
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Ovens
Jörg
J
Opelz
Gerhard
G
Sommerer
Claudia
C
Döhler
Bernd
B
Becker
Luis E
LE
Gross
Marie-Luise
ML
Waldherr
Rüdiger
R
Mieth
Markus
M
Sadeghi
Mahmoud
M
Schmidt
Jan
J
Langer
Robert M
RM
Zeier
Martin
M
Süsal
Caner
C
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
D017931:DNA Primers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents