Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection

Yi Tian Ting, P. Toby Coates, Hans Peter Marti, Amy C. Dunn, Richard M. Parker, John W. Pickering, Ralph W. Jack, Roslyn A. Kemp, Robert J. Walker, Alexander D. McLellan

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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.

Original languageEnglish
Pages (from-to)1071-1078
Number of pages8
JournalTransplantation
Volume89
Issue number9
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Keywords

  • HLA-DR
  • Renal transplant rejection
  • Soluble MHC

Cite this

Ting, Y. T., Coates, P. T., Marti, H. P., Dunn, A. C., Parker, R. M., Pickering, J. W., Jack, R. W., Kemp, R. A., Walker, R. J., & McLellan, A. D. (2010). Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection. Transplantation, 89(9), 1071-1078. https://doi.org/10.1097/TP.0b013e3181d15492