轻链型多发性骨髓瘤的N-糖谱特征及临床意义

Characteristic and clinical significance of N-glycan profile in light chain multiple myeloma

目的研究轻链型多发性骨髓瘤(LCMM)的血清N-糖谱特点及临床意义。方法采用DNA测序仪辅助的荧光糖电泳(DSA-FACE)对年龄和性别匹配的LCMM、IgG型多发性骨髓瘤(MM)患者和健康对照者的血清N-糖谱及其他实验室检查结果进行回顾性分析。结果 LCMM患者与健康对照者血清N-糖谱比较,Peak3(单半乳糖-α-1,6-核心岩藻糖基化二天线结构,NG1A2F)和Peak6(双半乳糖-α-1,6-核心岩藻糖基化二天线结构,NA2F)显著下降,而Peak5(双半乳糖二天线结构,NA2)显著升高;采用Peak3来验证其诊断效力,Peak3诊断LCMM的受试者工作特征(ROC)曲线下面积为0.943,最佳分界点5.15%对应的敏感性和特异性分别为88.1%和90.5%。LCMM与IgG型MM患者血清N-糖谱比较,Peak3和Peak6显著下降,Peak5显著升高;采用Peak3来验证其鉴别诊断效力,Peak3鉴别诊断LCMM的ROC曲线下面积为0.895,最佳分界点6.77%对应的敏感性和特异性分别为100.0%和78.6%。将3组N-糖谱结果与临床实验室指标进行相关性分析,Peak3的改变与血清IgG、总蛋白、M蛋白峰和血轻链比值的变化呈正相关,与白蛋白、血红蛋白和血小板的变化呈负相关;但Peak5的改变正好相反;Peak6与尿素、肌酐的变化呈负相关。结论 LCMM患者的血清N-糖谱有特征性改变,尤其是Peak3的改变与患者的低球蛋白血症、肾功能损害和病情的进展程度息息相关,有望成为新型的诊断和鉴别诊断LCMM的指标。而在LCMM的预后评价和监测中,N-糖谱的检测可以减少患者多次抽骨髓造成的身体伤害,并避免由于轻链多聚体的出现和肾功能的改变造成血清和尿中轻链检测的偏差。

Objective To investigate the characteristic and clinical significance of serum N-glycan profile in light chain multiple myeloma （ LCMM ）. Methods A retrospective analysis of serum N-glycan profile was performed in LCMM patients, IgG multiple myeloma（MM） patients and healthy controls with matched sex amd age by DNA sequence assisted, fluorophore-assisted carbohydrate electrophoresis （DSA-FACE）. Results Peak3 （ single agalaeto, core-alpha- 1,6-fucosylated biantennary, NG1A2F） and Peak6 （ bigalacto, core-alpha-1,6-fucosylated biantennary, NA2F） in LCMM patients were significantly lower than those in healthy controls, while Peak5 （bigalaeto, biantennary, NA2） was significantly higher. Using Peak 3 to verify the diagnosis efficiency, the area under the receiver operating characteristic （ROC） curve of Peak3 was 0. 943. The optimum diagnosis cut-off value was 5. 15% with sensitivity 88. 1% and specificity 90.5%. The decrease of Peak3 and Peak6 and the increase of Peak5 were found in LCMM patients, as compared with IgG MM patients. Using Peak3 to verify the differential diagnosis efficiency, the area under the ROC curve of Peak3 was 0. 895. The optimum differential diagnosis cut-off value was 6.77% with sensitivity 100.0% and specificity 78.6%. The changes of Peak3, contrary to PeakS, were positively correlated with IgG, total protein, M-spike and serum light chain ratio, and were negatively correlated with albumin, hemoglobin and platelet in the correlation analysis between serum N-glycan profile and routine laboratory parameters in the 3 groups, and the changes of Peak 6 were negatively correlated with urea and creatinine. Conclusions The characteristic change has taken place in the serum N-glyean profile of LCMM patients, especially Peak3, which is closely bound on the symptoms of hypoglobulinemia, kidney function injury and the progression of disease. Meanwhile, Peak3 may become a new biomarker for diagnosing and differentially diagnosing LCMM. During the prognosis evaluation and monitoring of LCMM, the determination of N-glycan profile avoids the hurt of drawing bone marrow and eliminates the detecting errors caused by polymers of light chain and kidney malfunction on the determination of serum and urine light chains.