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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.

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。

结论

在这项对常规临床环境中的 176 例患者队列的研究中,我们提供了真实世界 HLC 检测在识别 M 蛋白和监测 M 蛋白方面的临床实用性的证据,特别强调 IgA 单克隆丙种球蛋白病。

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