重/轻链检测作为多发性骨髓瘤诊断和随访的生物标志物。

Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple myeloma.

机构信息

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Clin Chim Acta. 2018 Apr;479:7-13. doi: 10.1016/j.cca.2018.01.010. Epub 2018 Jan 8.

DOI:10.1016/j.cca.2018.01.010

PMID:29324245

Abstract

BACKGROUND

The heavy-light chain (HLC) assay enables the accurate measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC measurements in the routine follow-up of intact immunoglobulin multiple myeloma (MM) patients.

METHODS

A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total immunoglobulin measurement, free light chain, and HLC assay. The correlations between M-protein levels and the HLC and FLC assay-derived parameters were examined and the clinical significance of the biomarkers was evaluated according to patients' status.

RESULTS

Involved HLC (iHLC) was the best biomarker correlating with M-protein concentration in both IgG and IgA MM, and could provide a surrogate marker substituting M-protein levels to follow the course of the disease, especially in β-migrating IgA M-proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC) yielded significantly different results among the various response categories in both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC in a stringent complete remission (sCR) sample was a marker of early non-symptomatic relapse.

CONCLUSION

In this study of a cohort of 176 patients in a routine clinical setting, we have provided evidence of the clinical utility of real world HLC assays for the identification of M-proteins and to monitor M-proteins with an emphasis on IgA monoclonal gammopathies.

摘要

背景

重轻链（HLC）检测可准确测量每种同种型特异性重链和轻链（即 IgGκ、IgGλ、IgAκ 和 IgAλ），并得出 HLC 对比值。然而，迄今为止，只有有限的数据验证了在完整免疫球蛋白多发性骨髓瘤（MM）患者的常规随访中连续 HLC 测量的有用性。

方法

对 115 例 IgG 和 61 例 IgA MM 患者的 36 例诊断性和 671 例治疗后血清进行毛细管区带电泳、免疫亚区电泳、总免疫球蛋白测定、游离轻链和 HLC 检测。检查 M 蛋白水平与 HLC 和 FLC 检测衍生参数之间的相关性，并根据患者的状态评估生物标志物的临床意义。

结果

受累 HLC（iHLC）是与 IgG 和 IgA MM 中 M 蛋白浓度相关性最好的生物标志物，可提供替代 M 蛋白水平的替代标志物来监测疾病的进程，尤其是在β迁移的 IgA M 蛋白中。iHLC 值的分布以及 HLC 对比值（rHLC）在 IgG 和 IgA MM 的各种反应类别中产生了明显不同的结果。此外，我们检测到 2 例在严格完全缓解（sCR）样本中异常 rHLC 是早期无症状复发的标志物。