Abstract
Plasma and urine glycosaminoglycans (GAGs) are long, linear sulfated polysaccharides that have been proposed as potential noninvasive biomarkers for several diseases. However, owing to the analytical complexity associated with the measurement of GAG concentration and disaccharide composition (the so-called GAGome), a reference study of the normal healthy GAGome is currently missing. Here, we prospectively enrolled 308 healthy adults and analyzed their free GAGomes in urine and plasma using a standardized ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method together with comprehensive demographic and blood chemistry biomarker data. Of 25 blood chemistry biomarkers, we mainly observed weak correlations between the free GAGome and creatinine in urine and hemoglobin or erythrocyte counts in plasma. We found a higher free GAGome concentration – but not a more diverse composition - in males. Partitioned by gender, we also established reference intervals for all detectable free GAGome features in urine and plasma. Finally, we carried out a transference analysis in healthy individuals from two distinct geographical sites, including data from the Lifelines Cohort Study, which validated the reference intervals in urine. Our study is the first large-scale determination of normal free GAGomes reference intervals in plasma and urine and represents a critical resource for future physiology and biomarker research.
Highlights
Glycosaminoglycans (GAGs) are a family of long linear polysaccharides consisting of repeating disaccharide units [1]
We took advantage of a standardized analytical method using ultra-highperformance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-MS/MS) [15] to analyze the urine and plasma free GAGomes in a Good Laboratory Practice (GLP)-compliant blinded central laboratory in two prospectively enrolled independent cohorts of 308 self-reported healthy subjects with comprehensive demographic and blood chemistry data
We found that no free GAGome feature showed any notables differences with respect to age in adults
Summary
Glycosaminoglycans (GAGs) are a family of long linear polysaccharides consisting of repeating disaccharide units [1]. Despite the potential role of GAGs for clinical applications, the measurements of the GAGome has been limited to very small sample sizes (ranging from 3 healthy donors in [7] to 25 in [6]), in predominantly retrospective and selected donors, with different analytical techniques performed within academic laboratories [3, 4, 6,7,8,9] These limitations are due to the historical lack of effective analytical methods until recently [10,11,12,13,14], which proved hard to standardize and expensive to run. We validated the proposed references intervals by transference analysis on two independent cohorts consisting of a total of 140 healthy individuals from two distinct geographical sites
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