Abstract
Identification and use of non-invasive biomarkers for kidney transplantation monitoring is an unmet need. A total of 121 biobanked sera collected from 111 unique kidney transplant (KT) patients (children and adolescent) and 10 age-matched healthy normal controls were used to profile serum proteins using semi-quantitative proteomics. The proteomics data were analyzed to identify panels of serum proteins that were specific to various transplant injuries, which included acute rejection (AR), BK virus nephropathy (BKVN), and chronic allograft nephropathy (CAN). Gene expression data from matching peripheral blood mononuclear cells were interrogated to investigate the association between soluble serum proteins and altered gene expression of corresponding genes in different injury phenotypes. Analysis of the proteomics data identified from different patient phenotypes, with criteria of false discovery rate <0.05 and at least twofold changes in either direction, resulted in a list of 10 proteins that distinguished KT injury from no injury. Similar analyses to identify proteins specific to chronic injury, acute injury, and AR after kidney transplantation identified 22, 6, and 10 proteins, respectively. Elastic-Net logistic regression method was applied on the 137 serum proteins to classify different transplant injuries. This algorithm has identified panels of 10 serum proteins specific for AR, BKVN, and CAN with classification rates 93, 93, and 95%, respectively. The identified proteins could prove to be potential surrogate biomarkers for routine monitoring of the injury status of pediatric KT patients.
Highlights
Organ transplantation is the treatment of choice for patients with organ failure [1]
To identify kidney transplant (KT) injury status, ANOVA was performed on proteomics data with the criteria of false discovery rate (FDR)
These proteins are associated with positive regulation of cholesterol esterification (FDR = 5.26E−10), plasma lipoprotein particle remodeling (FDR = 5.64E−08), regulation of response to wounding (FDR = 5.64E−08), and regulation of inflammatory response (FDR = 1.02E−07). (iii) Acute injury-specific proteins: we identified 6 differentially expressed proteins between patients with acute injury (AR and BKVN) and those with chronic injury (CAN and CNIT) or stable graft function (STA) (Table 2)
Summary
Organ transplantation is the treatment of choice for patients with organ failure [1]. The number of individuals in the waiting list outnumbers the organs that are available for transplantation [2]. Recent advancements in immunosuppressive therapy and surgical techniques have contributed in lowering early acute rejection (AR) events; long-term outcome of the transplanted organs is still not satisfactory [3]. Since transplanted organs continuously endure injuries that are immune and non-immune related, it is important to reduce such injuries. Serum Protein Biomarkers for Kidney Transplantation of the detailed mechanism of transplant injury would help in the proper management of transplanted organs for long-term survival [4]
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