A Targeted LC-MS/MS Assay of a Health Surveillance Panel and Its Application to Chronic Kidney Disease
Year: 2026
Type: article
Abstract: Robust and reproducible assays capable of specific and quantitative monitoring of multiple biologically important proteins amongst the thousands of human plasma proteins can potentially be used to distinguish health versus disease. In this study, we established an LC-MS assay to monitor a Health Surveillance Panel (HSP) comprising 60 circulating plasma proteins selected based on their broad biological functions and assay performance. Plasma samples were prepared for proteomic analysis in an automated process. A scheduled LC-MRM assay with a 30-minute 5% - 35% acetonitrile gradient and 50.5 minutes of total run time was used to quantify the 60 endogenous proteins by monitoring 364 transitions from 117 proteotypic peptides along with their stable isotopic labeled standard peptides in a single assay. For each proteotypic peptide, we selected a quantifier ion and at least two qualifier ions. The quantifier ions have a linear response over a 100-fold range, and the peak area ratios of the three peptide ions were consistent. As proof of concept, we evaluated the performance of our HSP assay in a case-control study of progressive chronic kidney disease (CKD). Reduced plasma concentrations of alpha-2-antiplasmin, antithrombin-III, and immunoglobulin heavy constant alpha 1 correlated with CKD indicated by reduced GFR with p values < 0.05. These results demonstrate that the HSP proteins can be accurately and reproducibly quantified with a high-quality multiplexed MRM assay and the HSP assay can detect disease-associated differences.
Source: Journal of Proteome Research
Authors: Qin Fu, Casey W. Courtelin Johnson, Lesley A. Inker, Jennifer E. Van Eyk, The CRIC Study Investigators
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: Center for Clinical and Translational Science, University of Illinois at Chicago, National Institutes of Health, School of Medicine, University of New Mexico, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1023715172, G1060671437, G1201304535, Clinical and Translational Science Institute, G1815451664, G197956372, G2375109747, Design and Validation of Easy-to-Adopt Mass Spectrometry Assays of Importance to Obesity, Continuation of the Chronic Renal Insufficiency Cohort (CRIC) Study, G2597979934, G3771679604, G5931204509, G742032275, G751309980, Institute for Clinical and Translational Research, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Prospective renal insufficiency cohort evaluation: PRICE, Continuation of the University of Illinois Chicago CRIC Clinical Center, Chronic Renal Insufficiency Cohort (CRIC) Study, G907906148
OpenAlex ID: W4408610170