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Reduced PARP1 as a Serum Biomarker for Graft Rejection in Kidney Transplantation.

ABSTRACT: A serum proteomics platform enabling expression Profiling in transplantation-associated clinical subsets gives an opportunity to identify non-invasive biomarkers that can accurately predict transplant outcome. In this study, we attempted to identify candidate serum biomarkers that could predict kidney allograft rejection/injury, regardless of its etiological and therapeutic heterogeneity. Using serum samples collected from kidney transplantation patients and healthy controls, we first employed Clontech-500 Ab microarrays to Profile acute rejection (AR) and chronic graft injury (CGI) versus stable graft function (SF) and normal kidneys (NK). Using GenePattern analysis of duplicate arrays on pooled samples, we identified gender-independent biomarkers PARP1, MAPK1, SRP54, DP1, and p57 (FDR ? 25%), the concordant downregulation of which represented a detrimental Profile common for both rejection/ injury types (AR-CGI). The reverse phase arrays qualified a 2-fold upregulation of PARP1 with an ROC of 0.87 in individual samples from patients with SF vs. AR-CGI rendering serum PARP1 as a biomarker for early prognosis. Ingenuity Pathways Analysis (IPA) connected PARP1 to some other markers (MAPK1), elucidating their possible interactions and connections to the immune response and graft-versus-host disease signaling. The downregulation of serum PARP1 in the damaged graft tissues, represents a perspective non-invasive marker, predicting the failing kidney graft, regardless of rejection/injury causes or gender. Thus, the successful identification of PARP1 as a bio-marker in limited patient cohorts demonstrates that serum proteomics platform empowered by the GenePattern- and IPA-based Bioinformatics algorithm can guarantee a successful development of the clinically applicable prognostic biomarker panel.

SUBMITTER: Srivastava M

PROVIDER: S-EPMC4780413 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Reduced PARP1 as a Serum Biomarker for Graft Rejection in Kidney Transplantation.

Srivastava Meera M Torosyan Yelizaveta Y Eidelman Ofer O Jozwik Catherine C Pollard Harvey B HB Mannon Rosyln R

Journal of proteomics & bioinformatics 20150101 2

A serum proteomics platform enabling expression Profiling in transplantation-associated clinical subsets gives an opportunity to identify non-invasive biomarkers that can accurately predict transplant outcome. In this study, we attempted to identify candidate serum biomarkers that could predict kidney allograft rejection/injury, regardless of its etiological and therapeutic heterogeneity. Using serum samples collected from kidney transplantation patients and healthy controls, we first employed C ...[more]

PMID: 26962294

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Project description:IntroductionAboriginal and Torres Strait Islander peoples (hereafter respectfully termed Indigenous Australians) experience a 3-fold increased risk of acute rejection after transplantation compared to non-Indigenous Australians. We investigated whether acute rejection explains the association between Indigenous status, infection-related deaths, and all-cause deaths after kidney transplantation, and whether acute rejection mediates the relationship between Indigenous status and overall graft loss.MethodsThis cohort study included all recipients who received their first kidney transplant between 2005 and 2018 in Australia, using data from the Australia and New Zealand Dialysis and Transplant registry. Multivariable Cox regression models determined the associations between Indigenous status, graft loss, infection-related deaths, and all-cause deaths. Mediation analyses examined if acute rejection mediated these relationships. Primary outcome was infection-related death. Secondary outcomes included all-cause death and overall graft loss.ResultsThere were 9993 patients (n = 390 (3.9%) Indigenous Australians) who received a kidney transplant between 2005 and 2018, and they were followed-up with for 56,876 patient-years. A total of 1165 died (12%) (211 infection-related deaths) and 1957 (20%) lost their allografts. Compared with non-Indigenous recipients, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for graft loss, infection-related deaths and all-cause deaths among Indigenous Australians were 2.27 (1.90-2.71), 3.01 (1.90-4.77) and 2.36 (1.89-2.94), respectively. The mediation analysis showed the association between Indigenous status and graft loss (but not infection-related death or all-cause death) was partially mediated by acute rejection (1.06 [1.03-1.09]), and the proportion of effects mediated by acute rejection was 0.10.ConclusionIndigenous Australians experienced a higher risk of graft loss, a relationship mediated partially through acute rejection. The higher risk of infection-related death was independent of acute rejection.

Dataset Information

Reduced PARP1 as a Serum Biomarker for Graft Rejection in Kidney Transplantation.

Publications

Reduced PARP1 as a Serum Biomarker for Graft Rejection in Kidney Transplantation.

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