Academic Journal
M-protein diagnostics in multiple myeloma patients using ultra-sensitive targeted mass spectrometry and an off-the-shelf calibrator
| العنوان: | M-protein diagnostics in multiple myeloma patients using ultra-sensitive targeted mass spectrometry and an off-the-shelf calibrator |
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| المؤلفون: | Wijnands, Charissa, Langerhorst, Pieter, Noori, Somayya, Keizer-Garritsen, Jenneke, Wessels, Hans J.C.T., Gloerich, Jolein, Bonifay, Vincent, Caillon, Hélène, Luider, Theo M., Van Gool, Alain J., Dejoie, Thomas, Vanduijn, Martijn M., Jacobs, Joannes F.M. |
| المصدر: | Wijnands , C , Langerhorst , P , Noori , S , Keizer-Garritsen , J , Wessels , H J C T , Gloerich , J , Bonifay , V , Caillon , H , Luider , T M , Van Gool , A J , Dejoie , T , Vanduijn , M M & Jacobs , J F M 2024 , ' M-protein diagnostics in multiple myeloma patients using ultra-sensitive targeted mass spectrometry and an off-the-shelf calibrator ' , Clinical Chemistry and Laboratory Medicine , vol. 62 , no. 3 , pp. 540-550 . https://doi.org/10.1515/cclm-2023-0781 |
| سنة النشر: | 2024 |
| الوصف: | Objectives: Minimal residual disease status in multiple myeloma is an important prognostic biomarker. Recently, personalized blood-based targeted mass spectrometry (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to measure minimal residual disease. However, quantification of MS-MRD requires a unique calibrator for each patient. The use of patient-specific stable isotope labelled (SIL) peptides is relatively costly and time-consuming, thus hindering clinical implementation. Here, we introduce a simplification of MS-MRD by using an off-the-shelf calibrator. Methods: SILuMAB-based MS-MRD was performed by spiking a monoclonal stable isotope labeled IgG, SILuMAB-K1, in the patient serum. The abundance of both M-protein-specific peptides and SILuMAB-specific peptides were monitored by mass spectrometry. The relative ratio between M-protein peptides and SILuMAB peptides allowed for M-protein quantification. We assessed linearity, sensitivity and reproducibility of SILuMAB-based MS-MRD in longitudinally collected sera from the IFM-2009 clinical trial. Results: A linear dynamic range was achieved of over 5 log scales, allowing for M-protein quantification down to 0.001 g/L. The inter-assay CV of SILuMAB-based MS-MRD was on average 11 %. Excellent concordance between SIL- and SILuMAB-based MS-MRD was shown (R 2 >0.985). Additionally, signal intensity of spiked SILuMAB can be used for quality control purpose to assess system performance and incomplete SILuMAB digestion can be used as quality control for sample preparation. Conclusions: Compared to SIL peptides, SILuMAB-based MS-MRD improves the reproducibility, turn-around-times and cost-efficacy of MS-MRD without diminishing its sensitivity and specificity. Furthermore, SILuMAB can be used as a MS-MRD quality control tool to monitor sample preparation efficacy and assay performance. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1515/cclm-2023-0781 |
| الاتاحة: | https://pure.eur.nl/en/publications/d994b584-a6cd-47e5-8913-16e750283841 https://doi.org/10.1515/cclm-2023-0781 https://pure.eur.nl/ws/files/115653819/M-protein_diagnostics_in_multiple_myeloma.pdf http://www.scopus.com/inward/record.url?scp=85174310738&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.78147947 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1515/cclm-2023-0781 |
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