title: The extent of HLA-DR expression on HLA-DR(+)  Tregs allows the identification of patients with clinically relevant borderline rejection.
abstract: Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA-DR(+) -Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA-DR expression of HLA-DR(+) -Tregs (MFI HLA-DR) were estimated in non transplanted volunteers, patients with end-stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord-R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord-R and ARF). Compared to patients with only Bord-R or only ARF, the suppressive activity of the total Treg cell pool was exclusively reduced in patients with clinically relevant Bord-R. In parallel, the HLA-DR MFI of the DR(+) -Treg subset was significantly decreased in these patients, due to a significantly lower proportion of DR(high+) -Tregs, which were shown to have the highest suppressive capacity within the total Treg pool. Our findings clearly demonstrate that the determination of the HLA-DR MFI of the HLA-DR(+) -Treg subset allows a highly sensitive, specific and non-invasive discrimination between patients with clinically relevant Bord-R (Bord and ARF) and patients with subclinical rejection or other causes of transplant failure.
authors.affiliation: Department of Nephrology, University of Heidelberg, D-69120 Heidelberg, Germany. matthias_schaier@med.uni-heidelberg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Schaier
authors.forename: Nicole
authors.initials: N
authors.lastname: Seissler
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Becker
authors.forename: Sebastian Markus
authors.initials: SM
authors.lastname: Schaefer
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Stefan
authors.initials: S
authors.lastname: Meuer
authors.forename: Friederike
authors.initials: F
authors.lastname: Hug
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Andrea
authors.initials: A
authors.lastname: Steinborn
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens