Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection.
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.
Ting
Yi Tian
YT
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Coates
P Toby
PT
Marti
Hans-Peter
HP
Dunn
Amy C
AC
Parker
Richard M
RM
Pickering
John W
JW
Jack
Ralph W
RW
Kemp
Roslyn A
RA
Walker
Robert J
RJ
McLellan
Alexander D
AD
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
D015415:Biomarkers; D006684:HLA-DR Antigens