Despite modern immunosuppression, renal allograft rejection remains a major contributor to graft loss. Novel biomarkers may help improve posttransplant outcomes through the early detection and treatment of rejection. Our objective is to provide an overview of proteomics, review recent discovery-based rejection studies, and explore innovative approaches in biomarker development.
Urine MMP7 was identified as a biomarker of subclinical and clinical rejection using two-dimensional liquid chromatography tandem–mass spectrometry (LC-MS/MS) and improved the overall diagnostic discrimination of urine CXCL10 : Cr alone for renal allograft inflammation. A novel peptide signature to classify stable allografts from acute rejection, chronic allograft injury, and polyoma virus (BKV) nephropathy was identified using isobaric tag for relative and absolute quantitation (TRAQ) and label-free MS, with independent validation by selected reaction monitoring mass spectrometry (SRM-MS). Finally, an in-depth exploration of peripheral blood mononuclear cells identified differential proteoform expression in healthy transplants versus rejection.
There is still much in the human proteome that remains to be explored, and further integration of renal, urinary, and exosomal data may offer deeper insight into the pathophysiology of rejection. Functional proteomics may be more biologically relevant than protein/peptide quantity alone, such as assessment of proteoforms or activity-based protein profiling. Discovery-based studies have identified potential biomarker candidates, but external validation studies are required.
aManitoba Centre for Proteomics and Systems Biology, University of Manitoba and Health Sciences Centre
bSection of Biomedical Proteomics
cSection of Nephrology, Department of Internal Medicine
dDepartment of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
eTransplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
Correspondence to Julie Ho, MD, FRCPC, Associate Professor, Internal Medicine & Immunology, Sections of Nephrology & Biomedical Proteomics, GE421C Health Sciences Centre, 820 Sherbrook Street, Winnipeg, MB, Canada R3A 1R9. Tel: +1 204 787 3115; fax: +1 204 787 3326; e-mail: firstname.lastname@example.org