单克隆免疫球蛋白病实验室筛查实践与筛查方法学比较

Comparison of laboratory screening practice and screening methodologies for monoclonal immunoglobulin disease

目的探讨游离轻链测定法、总轻链测定法以及毛细管电泳法对单克隆免疫球蛋白病的筛查效力,筛选费用与准确率的比值(费效比)低的测定方法。方法选择2018年3~12月于南方医科大学附属南海医院就诊的3213例患者为研究对象,采集患者外周血,离心后留取血清样本,另选择24例已确诊为多发性骨髓瘤患者血清样本作为阳性对照。采用游离轻链和总轻链试剂盒对研究对象血清样本进行检测,选取游离轻链法和总轻链法检出的轻链浓度异常升高且轻链κ/λ或λ/κ比值> 5的样本及24例阳性对照血清样本进行毛细血管电泳法检测,对游离轻链法检测出的轻链κ/λ或λ/κ比值> 10的样本同时进行毛细管电泳和免疫固定电泳,经免疫固定电泳确定轻链类型。计算费效比。结果总轻链法、游离轻链法、毛细管电泳法均能完全正确识别多发性骨髓瘤确诊病例(100%,24/24)。游离轻链法检出游离轻链κ/λ或λ/κ比值为40∶1~290∶1,筛出总κ或λ轻链水平浓度异常升高且轻链κ/λ或λ/κ比值> 10者123例,阳性率为3.8%(123/3 213),且均在毛细管电泳法中检出M蛋白峰;总轻链法检出轻链κ/λ或λ/κ比值为18∶1~257∶1,与游离轻链法相比,轻链比值降低(P <0.01);在筛查对象样本中,总κ或λ轻链水平异常且κ/λ或λ/κ比值> 10者39例,其中94.5%(35/37)的总轻链筛出异常值标本均在游离轻链法的116例异常样本覆盖范围之内。上述123例样本经免疫固定电泳确定为12例呈λ型M蛋白、103例呈κ型M蛋白,8例确定为多克隆性质。以免疫固定电泳为参比方法,游离轻链法、总轻链法以及毛细管电泳法检出异常免疫球蛋白的灵敏度分别为90.35%、62.50%、100.00%,特异度分别为99.58%、99.94%、100.00%,一致性分别为93.10%、97.15%、80.10%。毛细管电泳法费效比最低为30.0,游离轻链法费效比最高为451.1,总轻链法为76.9。结论游离轻链法和毛细管电泳法是良好的单克隆免疫球蛋白病筛查方法,且毛细管电泳法费效比最低。

Objective To investigate the efficacy of free light chain assay,total light chain assay and capillary electrophoresis in the screening of monoclonal immunoglobulin disease,and to screen out the method with the lowest ratio of testing cost to accuracy( cost-effectiveness ratio).Methods Three thousands two hundreds and thirteen patients who were hospitalized in Nanhai Hospital Affiliated to Southern Medical University from March to December 2018 were selected as the research subjects.Peripheral blood samples were collected,and serum samples were collected after centrifugation.Serum samples of 24 patients with multiple myeloma were taken as positive control.The free light chain and total light chain kits were used to detect serum samples.The serum samples with abnormally high light chain concentration and light chain κ/λ or λ/κ ratio > 5 detected by free light chain and total light chain kits and 24 positive control were selected for capillary electrophoresis detection,and the serum samples with abnormally high light chain concentration and light chain κ/λ or λ/κ ratio > 10 were selected for capillary electrophoresis and immunofixation electrophoresis,the type of light chain was determined by immunofixation electrophoresis.The cost-effectiveness ratio was calculated.Results The total light chain assay,free light chain assay,and capillary electrophoresis method all could complete correctly identify the confirmed cases of multiple myeloma( 100%,24/24).The free light chain assay detected that the ratio of free light chain κ/λ or λ/κ was from 40∶1 to 290∶1,and the total κ or λ light chain concentration abnormally increased and the light chain κ/λ or λ/κ > 10 was screened out in123 patients.The positive rate was 3.8%( 123/3 213),and the M protein peak was detected in capillary electrophoresis;the light chain κ/λ or λ/κ ratio was from 18∶1 to 257∶1 detected by the total light chain method,the light chain ratio detected by the total light chain assay was statistically decreased compared with that detected by the free light chain method( P <0.01).In the sample of screening subjects,the total κ or λ light chain level abnormal and κ/λ or λ/κ ratio > 10 were in 39 cases,among which 94.5%( 35/37) with the total light chain screened out abnormal value samples were all within the coverage of 116 abnormal samples of free light chain assay.According to immunofixation electrophoresis,12 samples were identified as λ M protein,103 samples were κ M protein,and 8 samples were polyclonal.The sensitivity of free light chain assay,total light chain assay and capillary electrophoresis assay were 90.35%,62.50% and 100.00%;the specificity were99.58%,99.94%,100.00%;and the consistency was 93.10%,97.15% and 80.10%.The cost-effectiveness ratio of capillary electrophoresis was the lowest as 30.0;the cost-effectiveness ratio of the free light chain assay was the highest as451.1;the cost-effectiveness ratio of the total light chain assay was 76.9.Conclusion Free light chain assay and capillary electrophoresis are both good screening methods for monoclonal immunoglobulin disease,however the cost-effectiveness ratio of the latter is the lower.