Evaluation of biomarker discovery approaches to detect protein biomarkers of acute renal allograft rejection.
Management of host responses to allografts by immunosuppressive therapy is the cornerstone of transplantation medicine, but it is still deficient in one important element: biomarkers that are readily accessible and predict the fate of the transplant early, specifically, and reliably. Using a Brown Norway (BN)-to-Lewis rat renal allograft model of kidney transplantation, this study aims at evaluating two proteomic approaches to discover biomarkers for acute rejection: SELDI-MS technology and 2D gel electrophoresis combined with mass spectrometry. Several novel potential serum biomarkers have been identified for follow up. Overall, the conclusion is that apparently at the serum protein level, dramatic changes only occur at a stage where kidney function is already severely affected. Multivariate analysis of serum profiles suggests that there is an ensemble of subtle changes, comprising a proteomic signature of acute rejection at an early stage, a more detailed evaluation of which might provide novel opportunities for the diagnosis of acute rejection. Profiling of the excreted proteins indicates that urine might even present the earliest signs of the rejection process.
Voshol
Hans
H
Novartis Institutes for BioMedical Research, Genome and Proteome Sciences and Transplantation & Immunology Therapeutic Area, CH-4002 Basel, Switzerland. johannes.voshol@novartis.com
Brendlen
Nathalie
N
Müller
Dieter
D
Inverardi
Bruno
B
Augustin
Angélique
A
Pally
Charles
C
Wieczorek
Grazyna
G
Morris
Randall E
RE
Raulf
Friedrich
F
van Oostrum
Jan
J
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015180:Electrophoresis, Gel, Two-Dimensional; D006084:Graft Rejection / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D013058:Mass Spectrometry; D040081:Protein Array Analysis; D051381:Rats; D013997:Time Factors
D015415:Biomarkers