Non-Invasive Proteomics to Detect Biomarkers for Kidney Allograft Dysfunction

M. Watson,¹ M. Srivastava,³ D. Little,¹ O. Eidelman,³ R. Nee,¹ A. Bera,³ J. Karaian,³ D. Oliver,¹ H. Pollard,³ R. Jindal.²

¹Nephrology, USU-Walter Reed, Bethesda, MD
²Surgery, USU-Walter Reed, Bethesda, MD
³Anamtomy, Physiology and Genetics, USU-School of Medicine, Bethesda, MD.

Meeting: 2018 American Transplant Congress

Abstract number: A5

Keywords: Biopsy, Kidney transplantation, Rejection, Renal dysfunction

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Background: Non-invasive biomarkers are needed for monitoring patients to predict early acute rejection (AR). We hypothesized that protein biomarkers released from rejecting allograft tissues can be detected early in the systemic circulation and obviate the need for a biopsy.

Methods: Serum from renal transplant (RT) patients requiring kidney biopsy (group 1, n=22), RT patients with stable allograft function (group 2, n=25), chronic kidney disease patients awaiting transplant (group 3, n=25) and healthy individuals (group 4, n=25) were collected and labeled with the fluorescent dye Cy3, and assayed on 250 feature phosphoprotein microarray platform from Full Moon Biosystems, Inc. Cy5 labeled pooled serum was used to correct for spot variability. Array data were normalized by using the median signal of all 80 proteins on the array (to correct for loading variability). Data were presented as the average signal of 6 spots divided by the 80 protein median.

Results: Higher serum concentrations of proteins identified by bioinformatics analysis in group 1 vs. 2 included P38 MAPK and ubiquitin (p<0.02). Proteins significantly elevated in group 1 vs. 3 (p<0.01) were AKT, IkB-beta, NFkB-p100, IkB-alpha, Histone-H3.1, IKK alpha, BTK, P38 MAPK, PKC zeta, AKT2, CBP (inter), and CK2-b. Elevated proteins in group 2 vs. 3 (p<0.02) were Ikk beta, PKC zeta, NFkB-p100, PKR, and Elk-1. Phosphorylated proteins, phospho-species of NFkB-p105/p50 and BTK were higher in group 1 vs. 3 (p<0.01). Phospho-species elevated in group 2 vs. 3 included IKK beta, PKC zeta and Histone-H3.1 (p<0.01).

Conclusion:These novel serum analytes are candidates for a quantitative serum proteomic signature for renal allograft AR. This subset of markers suggests pro-inflammatory processes contribute to AR and may provide a non-invasive tool for surveillance of RT recipients. Validation of these biomarkers will require a larger, multi-center cohort.

The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army, the Department of Defense, The United States Government or the Uniformed Services University. No financial conflict of interest exists.

CITATION INFORMATION: Watson M., Srivastava M., Little D., Eidelman O., Nee R., Bera A., Karaian J., Oliver D., Pollard H., Jindal R. Non-Invasive Proteomics to Detect Biomarkers for Kidney Allograft Dysfunction Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Watson M, Srivastava M, Little D, Eidelman O, Nee R, Bera A, Karaian J, Oliver D, Pollard H, Jindal R. Non-Invasive Proteomics to Detect Biomarkers for Kidney Allograft Dysfunction [abstract]. https://atcmeetingabstracts.com/abstract/non-invasive-proteomics-to-detect-biomarkers-for-kidney-allograft-dysfunction/. Accessed November 21, 2024.

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