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Mining the serum proteome for non-invasive monitoring of kidney allograft rejection
2nd International Conference and Exhibition on Pharmaceutics and Advanced Drug Delivery Systems
July 05-06, 2019 | Paris, France
Meera Srivastava, Ofer Eidelman, Alakesh Bera, Maura Watson, Dustin Little, Robert Nee, Michael Ekund,Harvey Pollard and Rahul Mss Jindal
Uniformed Services University, USA
Posters & Accepted Abstracts : Asian J Biomed Pharmaceut Sci
Abstract:
Introduction: We hypothesized that protein biomarkers
released from rejecting allograft tissues can be detected
early in the systemic circulation.
Approach: We outline our modifications in the on-going
search for biomarker panel that could accurately predict
complications during kidney allograft rejection. In order
to increase validity of identified allograft rejection-specific
biomarkers, we used high-throughput protein array platforms
and applied Systems Biology approach.
Methods: Serum samples were collected prospectively from 4
groups of patients (n=25 in each group); Group 1: recipients of
kidney transplant requiring kidney biopsy for renal dysfunction,
Group 2: transplant recipients with stable function, Group 3:
chronic kidney disease patients awaiting transplant, and Group
4: healthy individuals. Serum was labelled with the fluorescent
dye Cy3 and assayed on phosphoprotein microarray platform
from Full moon Biosystems. For subsequent validation by
quantitative Reverse Capture Protein Microarray platform,
we used individual serum samples that were spotted in
serial dilutions on a glass slide and probed with the specific
antibodies for predicted biomarker proteins and correlated
with the severity of the disease.
Results: Using bioinformatics algorithms, we were able to
identify multiple candidate graft rejection-specific biomarkers.
Lower levels of Ubiquitin, p38MAPK, histone H3.1 and Tak1 and
higher levels of ATM, p38MAPK, HDAC8, SAPK/JNK, GSK3a-b,
NFkappa B and RelB pointing to an altered p53 Signaling
pathway were associated with group 3 and group 1 patient
serum. Among the tested phosphorylated proteins, phosphospecies
of SAPK/JNK and RelB were elevated in group 2 vs.
group 3 and group 1.
Conclusion: Data suggested that these novel analytes in the
serum, together or independently, may constitute a robust and
quantitative serum proteomic signature for rejection of renal
allografts. We conclude that detection of allograft rejection by
affinity proteomics offers a promising non-invasive tool for the
surveillance and early detection of kidney allograft rejection.
Biography:
E-mail:
meera.srivastava@usuhs.eduPDF HTML