Identification of Plasma Protein Biomarkers of Acute Renal Allograft Rejection.
1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
2Department of Biostatistics, University of California Los Angeles, Los Angeles, CA
Meeting: 2017 American Transplant Congress
Abstract number: D26
Keywords: Inflammation, Kidney transplantation, Lipoproteins, Rejection
Session Information
Session Name: Poster Session D: Diagnostics/Biomarkers Session II
Session Type: Poster Session
Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background & Aim: Upon presentation of clinical symptoms, renal transplant recipients routinely undergo needle core biopsy to diagnose acute graft rejection. This procedure is invasive and associated with patient morbidity. The aim of this study was to validate the use of plasma proteins as a minimally invasive and cost-effective panel of biomarkers for the diagnosis of renal allograft rejection.
Methods: We selected 8 proteins, previously identified by mass spectrometry as differentially present at the time of rejection in a pilot study on 18 patients with acute rejection, to be tested by ELISA in the plasma of 164 adult renal transplant recipients. The cohort included 91 non-rejectors and 73 rejectors, the latter sampled at the time of rejection (-7/+3 days of a positive biopsy) or after the event (>30 days after the positive biopsy). The non-rejectors were sampled +/- 30 days from the negative biopsy.
Results: We were able to confirm statistically significant differences both cross-sectionally (rejectors vs non-rejectors) and longitudinally (rejection vs post-rejection) in Apolipoprotein A1 (ApoA1), as we previously published. In addition, we found statistically significant differences in alpha-2-Macroglobulin (A2M), C1-inhibitor and ITIH4 cross-sectionally, and in Alpha-1-Antichymotrypsin and ApoA1 longitudinally, suggesting that these proteins are altered at the time of rejection and then return to baseline levels upon resolution. Next, we sought to determine whether combinations of these markers could be used to classify patients as rejecting or non-rejecting. Multivariate logistic regression and CART analyses demonstrated that a combination of these proteins might be used to this aim, with ApoA1, A2M and C4 being the best predictors (AUC = 0.785).
Conclusion: Several of the plasma proteins we identified could be used as a panel to rule out acute cellular renal allograft rejection. Our data warrant further validation of this new method in a larger independent renal transplant cohort.
CITATION INFORMATION: Rossetti M, Fitzpatrick C, Harre N, Zheng Y, Mercer N, Sunga G, Gjertson D, Reed E. Identification of Plasma Protein Biomarkers of Acute Renal Allograft Rejection. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Rossetti M, Fitzpatrick C, Harre N, Zheng Y, Mercer N, Sunga G, Gjertson D, Reed E. Identification of Plasma Protein Biomarkers of Acute Renal Allograft Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/identification-of-plasma-protein-biomarkers-of-acute-renal-allograft-rejection/. Accessed May 18, 2025.« Back to 2017 American Transplant Congress