دورية أكاديمية
The Common H202D Variant in GDF-15 Does Not Affect Its Bioactivity but Can Significantly Interfere with Measurement of Its Circulating Levels.
| العنوان: | The Common H202D Variant in GDF-15 Does Not Affect Its Bioactivity but Can Significantly Interfere with Measurement of Its Circulating Levels. |
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| المؤلفون: | Karusheva, Yanislava, Ratcliff, Matthew, Mörseburg, Alexander, Barker, Peter, Melvin, Audrey, Sattar, Naveed, Burling, Keith, Backmark, Anna, Roth, Robert, Jermutus, Lutz, Guiu-Jurado, Esther, Blüher, Matthias, Welsh, Paul, Hyvönen, Marko, O'Rahilly, Stephen |
| بيانات النشر: | Department of Clinical Biochemistry //dx.doi.org/10.1093/jalm/jfac055 J Appl Lab Med Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Humans, Growth Differentiation Factor 15, Immunoassay, Enzyme-Linked Immunosorbent Assay |
| الوصف: | BACKGROUND: There is growing interest in the measurement of growth differentiation factor 15 (GDF-15) in a range of disorders associated with cachexia. We undertook studies to determine whether a common histidine (H) to aspartate (D) variant at position 202 in the pro-peptide (position 6 in the mature peptide) interfered with its detection by 3 of the most commonly used immunoassays. METHODS: Three synthetic GDF-15-forms (HH homo-, HD hetero-, and DD-homodimers) were measured after serial dilution using Roche Elecsys®, R&D QuantikineTM ELISA, and MSD R&D DuoSet® immunoassays. GDF-15 concentrations were measured by the Roche and the MSD R&D immunoassays in 173 genotyped participants (61 HH homozygotes, 59 HD heterozygotes, and 53 DD homozygotes). For the comparative statistical analyses of the GDF-15 concentrations, we used non-parametric tests, in particular Bland-Altman difference (bias) plots and Passing-Bablok regression. The bioactivity of the 2 different homodimers was compared in a cell-based assay in HEK293S-SRF-RET/GFRAL cells. RESULTS: The Roche assay detected H- and D-containing peptides similarly but the R&D reagents (Quantikine and DuoSet) consistently underreported GDF-15 concentrations in the presence of the D variant. DD dimers had recoveries of approximately 45% while HD dimers recoveries were 62% to 78%. In human serum samples, the GDF-15 concentrations reported by the R&D assay were a median of 4% lower for HH, a median of 36% lower for HD, and a median of 61% lower for DD compared to the Roche assay. The bioactivities of the HH and DD peptides were indistinguishable. CONCLUSIONS: The D variant of GDF-15 substantially affects its measurement by a commonly used immunoassay, a finding that has clear implications for its interpretation in research and clinical settings. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/octet-stream |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/337923Test |
| DOI: | 10.17863/CAM.85329 |
| الإتاحة: | https://doi.org/10.17863/CAM.85329Test https://www.repository.cam.ac.uk/handle/1810/337923Test |
| حقوق: | All Rights Reserved ; http://www.rioxx.net/licenses/all-rights-reservedTest |
| رقم الانضمام: | edsbas.A5A0F3B7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.85329 |
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