MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients.
MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients.
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DOI：
10.1038/s41408-021-00444-0
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发表时间：
2021-03-04
影响因子：
12.8
通讯作者：
Dispenzieri A
中科院分区：
文献类型：
--
作者：
Mellors PW;Dasari S;Kohlhagen MC;Kourelis T;Go RS;Muchtar E;Gertz MA;Kumar SK;Buadi FK;Willrich MAV;Lust JA;Kapoor P;Lacy MQ;Dingli D;Hwa Y;Fonder A;Hobbs M;Hayman S;Warsame R;Leung NR;Lin Y;Gonsalves W;Siddiqui M;Kyle RA;Rajkumar SV;Murray DL;Dispenzieri A
基于免疫富集的基质辅助激光解吸电离飞行时间质谱法（MALDI-TOF-MS）（称为MASS-FIX）在血清单克隆蛋白的检测和同种型分型方面优于免疫固定法，包括上级灵敏度和特异性、区分治疗性单克隆抗体的能力以及快速鉴定轻链（LC）N-糖基化。我们确定了自2018年以来在我们机构进行MASS-FIX的6315例患者。其中，4118例（65%）患有各种浆细胞疾病（PCD）（包括具有临床意义的罕见单克隆丙种球蛋白病）的患者MASS-FIX呈阳性。221例（5%）MASS-FIX阳性患者有LC N-糖基化证据，与其他PCD相比，在IgM重链同种型、kappa LC同种型以及免疫球蛋白轻链（AL）淀粉样变性和冷凝集素病（CAD）诊断中更常见。这项横断面研究描述了在常规临床实践中接受MASS-FIX的最大患者队列。我们的研究结果证明了该检测的广泛应用，并证实LC N-糖基化应在适当的临床背景下提示对AL淀粉样变性和CAD的怀疑。
Immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, offers several advantages over immunofixation for the detection and isotyping of serum monoclonal protein, including superior sensitivity and specificity, the ability to differentiate therapeutic monoclonal antibodies, and the rapid identification of light chain (LC) N-glycosylation. We identified 6315 patients with MASS-FIX performed at our institution since 2018. Of these, 4118 patients (65%) with a wide array of plasma cell disorders (PCD), including rare monoclonal gammopathies of clinical significance, had a positive MASS-FIX. Two-hundred twenty-one (5%) of the MASS-FIX positive patients had evidence of LC N-glycosylation, which was more commonly identified in IgM heavy chain isotype, kappa LC isotype, and in diagnoses of immunoglobulin light chain (AL) amyloidosis and cold agglutinin disease (CAD) compared to other PCD. This cross-sectional study describes the largest cohort of patients to undergo MASS-FIX in routine clinical practice. Our findings demonstrate the widespread utility of this assay, and confirm that LC N-glycosylation should prompt suspicion for AL amyloidosis and CAD in the appropriate clinical context.