毛细管电泳在良恶性单克隆球蛋白血症的诊断及鉴别诊断中的应用

Application of capillary electrophoresis in the diagnosis and differential diagnosis of benign and malignant monoclonal gammopathies

目的:评估毛细管电泳在良恶性单克隆球蛋白血症(MG)的诊断及鉴别诊断中的应用价值。方法:回顾分析青岛大学附属医院2016年1月至2020年6月门诊及住院初诊患者2445例的毛细管电泳检测结果,通过青岛大学附属医院临床大数据库收集患者的临床诊断等信息。多组间单克隆球蛋白含量差异比较采用Kruskal-Wallis等级秩和检验,通过受试者工作特征(ROC)曲线分析各型单克隆球蛋白的诊断敏感度及特异度,采用约登指数计算截断值。结果:2445例初诊患者中,单克隆球蛋白阳性1183例,其中诊断为恶性MG 944例,未定性的单克隆γ球蛋白血症(MGUS)174例,具有肾脏意义的单克隆球蛋白血症(MGRS)65例。单克隆球蛋白分型比例由高到低为IgG-κ型、IgG-λ型、IgA-λ型、IgA-κ型、游离λ轻链型、游离κ轻链型、IgM-κ型、双克隆型及IgM-λ型。恶性MG组的IgG、IgA、IgM及游离轻链型(FLC)型单克隆球蛋白含量均高于MGUS组,差异有统计学意义(P<0.01)。恶性MG组与MGRS组比较,IgG及IgA型单克隆球蛋白含量差异有统计学意义(P<0.01)。ROC曲线分析IgG、IgA、IgM及FLC型单克隆球蛋白对恶性MG均有较好的诊断效能(P<0.01),ROC曲线下面积分别为0.947(95%CI 0.926~0.968)、0.930(95%CI 0.895~0.966)、0.844(95%CI 0.722~0.967)和0.865(95%CI 0.781~0.950)。IgG型单克隆球蛋白截断值为14.24 g/L,诊断敏感度及特异度为88.5%和90.1%;IgA型单克隆球蛋白截断值为8.88 g/L,敏感度及特异度为87.9%和81.4%;IgM型单克隆球蛋白截断值为26.93 g/L,敏感度及特异度为64.4%和90.9%;FLC型单克隆球蛋白截断值为7.08 g/L,诊断敏感度85.9%,特异度77.8%。结论:毛细管电泳免疫分型技术可用于多发性骨髓瘤、非霍奇金淋巴瘤等恶性MG的诊断,也可用于MGUS、MGRS疾病的筛查及追踪;血清单克隆球蛋白水平可有效鉴别良恶性MG。

Objective:To evaluate the value of capillary electrophoresis in the diagnosis and differential diagnosis of benign and malignant monoclonal gammopathies(MGs).Methods:A retrospective analysis of the capillary electrophoresis test results of 2445 newly diagnosed patients at the Affiliated Hospital of Qingdao University from January 2016 to June 2020 was carried out.Capillary zone electrophoresis and immunosubtractive assay were used to detect serum monoclonal protein(MP).The clinical diagnosis and other information of the patients were collected from the clinical database of the Affiliated Hospital of Qingdao University.Kruskal-Wallis rank sum test was used to compare the different amount of monoclonal protein among multiple groups.Receiver operator characteristic curve(ROC)was used to analyze the diagnostic sensitivity and specificity of the monoclonal protein of each type.Youden index was used to calculate the cut-off values.Results:Among the 2445 patients,1183 were positive for monoclonal protein,of which 944 cases were diagnosed as malignant MG,174 were monoclonal gammopathy of undetermined significance(MGUS),and 65 cases were monoclonal gammopathy of renal significance(MGRS).The percentages of M protein types from high to low is immunoglobulin G(IgG)-κ,IgG-λ,IgA-λ,IgA-κ,freeλlight chain,freeκlight chain,IgM-κ,double clone,and IgM-λ.The levels of MP of IgG,IgA,IgM and FLC in the malignant MG group were all higher than those in the MGUS group,with statistical significance(P<0.01).The MP levels of IgG and IgA types in malignant MG group were higher than that in MGRS group(P<0.01).ROC curve analysis showed that the MP of IgG,IgA,IgM and FLC types had good diagnostic efficacy for malignant MG(P<0.01),and their AUC values were 0.947(95%CI 0.926-0.968),0.930(95%CI 0.895-0.966),0.844(95%CI 0.722-0.967)and 0.865(95%CI 0.781-0.950),respectively.For IgG,the cut-off value was 14.24 g/L,and the diagnostic sensitivity and specificity were 88.5%and 90.1%,respectively.The cut-off value of IgA was 8.88 g/L,and the sensitivity and specificity of IgA were 87.9%and 81.4%,respectively.For IgM,the cut-off value was 26.93 g/L,and the sensitivity was 64.4%and the specificity was 90.9%.For FLC,the cut-off value,diagnostic sensitivity,and specificity was 7.08 g/L,85.9%,and 77.8%,respectively.Conclusions:Capillary electrophoresis immunotyping technique can be used to diagnose malignant MG such as multiple myeloma(MM)and non-Hodgkin′s lymphoma(NHL),as well as to screen and track diseases like MGUS and MGRS.Serum MP level can be used to distinguish malignant MG from benign MG effectively.