title: Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection.
abstract: BACKGROUND.: Urine is a potentially rich source of biomarkers for monitoring kidney dysfunction. In this study, we have investigated the potential of soluble human leukocyte antigen (sHLA)-DR in the urine for noninvasive monitoring of renal transplant patients. METHODS.: Urinary soluble HLA-DR levels were measured by sandwich enzyme-linked immunosorbent assay in 103 patients with renal diseases or after renal transplantation. sHLA-DR in urine was characterized by Western blotting and mass spectrometry. RESULTS.: Acute graft rejection was associated with a significantly elevated level of urinary sHLA-DR (P<0.0001), compared with recipients with stable graft function or healthy individuals. A receiver operating characteristic curve analysis showed the area under the curve to be 0.88 (P<0.001). At a selected threshold, the sensitivity was 80% and specificity was 98% for detection of acute renal transplant rejection. sHLA-DR was not exosomally associated and was of lower molecular weight compared with the HLA-DR expressed as heterodimer on the plasma membrane of antigen-presenting cells. CONCLUSIONS.: sHLA-DR excreted into urine is a promising indicator of renal transplant rejection.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: Yi Tian
authors.initials: YT
authors.lastname: Ting
authors.forename: P Toby
authors.initials: PT
authors.lastname: Coates
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Marti
authors.forename: Amy C
authors.initials: AC
authors.lastname: Dunn
authors.forename: Richard M
authors.initials: RM
authors.lastname: Parker
authors.forename: John W
authors.initials: JW
authors.lastname: Pickering
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Jack
authors.forename: Roslyn A
authors.initials: RA
authors.lastname: Kemp
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.forename: Alexander D
authors.initials: AD
authors.lastname: McLellan
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D006684:HLA-DR Antigens / Q000097:blood / Q000652:urine*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008875:Middle Aged; D012995:Solubility
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens