两种游离轻链检测方法的比较：游离轻链比值作为意义未明的单克隆丙种球蛋白病（MGUS）进展风险因素的性能

Comparison of 2 Free Light Chain Assays: Performance of the Free Light Chain Ratio as a Risk Factor for MGUS Progression.

作者信息

Wang Qian, Andress Benjamin D, Pazdernik Vanessa M K, Larson Dirk R, Coker Jonathan D, Dasari Surendra, Rajkumar Vincent, Dispenzieri Angela, Murray David L, Willrich Maria Alice V

机构信息

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.

Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States.

出版信息

Clin Chem. 2024 Oct 3;70(10):1268-1278. doi: 10.1093/clinchem/hvae124.

DOI:10.1093/clinchem/hvae124

PMID:39206639

Abstract

BACKGROUND

New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS).

METHODS

Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2).

RESULTS

There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit.

CONCLUSIONS

The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay.

摘要

背景

新型免疫球蛋白游离轻链（FLC）检测方法已问世。尽管存在分析差异，但似乎可以使用不同检测方法生成的游离轻链比值（FLCr），并应用相似的切点来诊断多发性骨髓瘤。对于意义未明的单克隆丙种球蛋白病（MGUS）患者，能否使用不同检测方法进行风险分层仍不清楚。

方法

对923例诊断为MGUS的患者，使用西门子BNII仪器上的散射比浊法FreeLite（Binding Site）检测和Dynex DS2 ELISA分析仪上的Sebia FLC检测来检测FLC。对患者进行数十年的随访，观察其进展为任何浆细胞异常增殖性疾病（PCD）的情况。运用试剂盒说明书中的参考区间（RI）和一种名为主成分2（PC2）的新指标，通过两种检测方法评估Mayo MGUS进展风险分层模型（M蛋白峰>1.5 g/dL；非IgG同种型且FLCr异常）。