Comparison of Liquid Chromatography–Tandem Mass Spectrometry and Sandwich ELISA for Determination of Keratan Sulfate in Plasma and Urine

Department of Pediatrics, School of Medicine, Saint Louis University, St. Louis, MO, USA.
Biomarker insights 06/2011; 6(2):69-78. DOI: 10.4137/BMI.S7451
Source: PubMed


Mucopolysaccharidosis IVA (MPS IVA) leads to skeletal dysplasia through excessive storage of chondroitin-6-sulfate and keratan sulfate (KS). KS is synthesized mainly in cartilage and released into circulation, making it a critical biomarker for MPS IVA to evaluate clinical course and effectiveness of therapies. Therefore, an accurate and sensitive method is required to measure KS levels.
Using sandwich ELISA and liquid chromatography tandem mass spectrometry (LC/MS/MS) assays, we measured KS levels in blood and urine from MPS IVA patients and healthy controls to evaluate comparability of results. Blood (patients, n = 110; controls, n = 364) and urine (patients, n = 103; controls, n = 326) specimens were obtained.
Plasma and urine KS measurements in patients were age-dependent and higher than age-matched controls. We observed a moderate correlation (r = 0.666; P < 0.001) between urine KS measurements and a weak correlation (r = 0.333; P = 0.002) between plasma KS measurements by ELISA and LC/MS/MS methods in patients. No correlation was found between plasma KS measurements in controls. The difference between KS measurements assayed by LC/MS/MS and ELISA was greater in controls than in patients. A moderate correlation between blood and urine KS measurements in the same individual was observed.
These findings indicate that both methods to measure blood and urine KS are suitable for diagnosis, monitoring therapies, and longitudinal assessment of the disease course in MPS IVA, but the LC/MS/MS method measures over 10 times more KS present in body fluids.

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    • "While some research suggests that blood KS may be an additional biomarker of interest in MPSIVA patients, further research is needed to understand its use and determine the best methods for analysis (Oguma et al 2007; Martell et al 2011; Hintze et al 2011 "
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