Department of Neurology, Erasmus MC University Medical Center , Rotterdam 3015 GE, The Netherlands.
Department of Clinical Chemistry, Erasmus MC University Medical Center , Rotterdam 3015 GE, The Netherlands.
J Proteome Res. 2018 Mar 2;17(3):1326-1333. doi: 10.1021/acs.jproteome.7b00890. Epub 2018 Feb 15.
M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass-spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab, and nivolumab). This assay can target proteotypic M-protein peptides as well as unique peptides derived from therapeutic monoclonal antibodies. We address the sensitivity in M-protein diagnostics and show that our mass-spectrometry assay is more than two orders of magnitude more sensitive than conventional M-protein diagnostics. The use of stable isotope-labeled peptides allows absolute quantification of the M-protein and increases the potential of assay standardization across multiple laboratories. Finally, we discuss the position of mass-spectrometry assays in monitoring minimal residual disease in multiple myeloma, which is currently dominated by molecular techniques based on plasma cell assessment that requires invasive bone marrow aspirations or biopsies.
在多发性骨髓瘤患者接受治疗性单克隆抗体治疗时，M 蛋白诊断可能会受到影响。传统技术通常无法区分 M 蛋白和给予患者的治疗性单克隆抗体。这可能会妨碍正确的反应评估，并导致过度治疗。我们开发了一种基于血清的靶向质谱检测法来检测 M 蛋白，即使在存在三种治疗性单克隆抗体（达雷妥尤单抗、伊匹单抗和纳武单抗）的情况下也是如此。该检测法可以靶向 M 蛋白的特征肽段，以及来自治疗性单克隆抗体的独特肽段。我们解决了 M 蛋白诊断中的灵敏度问题，并表明我们的质谱检测法比传统的 M 蛋白诊断法灵敏两个数量级以上。稳定同位素标记肽的使用允许对 M 蛋白进行绝对定量，并增加了跨多个实验室进行检测标准化的潜力。最后，我们讨论了质谱检测法在多发性骨髓瘤微小残留病监测中的地位，目前该监测主要基于基于浆细胞评估的分子技术，这些技术需要侵入性的骨髓抽吸或活检。
