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螺旋-II 表位:基于无效胶原序列的软骨生物标志物的警示故事。

The Helix-II epitope: a cautionary tale from a cartilage biomarker based on an invalid collagen sequence.

机构信息

University of Washington, Department of Orthopaedics and Sports Medicine, 1959 NE Pacific Street, HSB BB1052, P.O. Box 356500, Seattle, WA 98195-6500, USA.

出版信息

Osteoarthritis Cartilage. 2009 Apr;17(4):423-6. doi: 10.1016/j.joca.2009.02.005. Epub 2009 Mar 5.

Abstract

OBJECTIVE

An apparent database error in the sequence underlying the Helix-II cartilage biomarker immunoassay was investigated at the protein level.

METHODS AND RESULTS

Tandem mass spectrometry established the peptide sequence ERGETGPPGPA in human type II collagen, not ERGETGPPGTS used to generate the antibody for the Helix-II assay.

CONCLUSIONS

Recent reports in which the Helix-II assay was applied to urine or serum as a marker of cartilage collagen degradation need to be re-evaluated since the epitope does not occur in cartilage type II collagen. Based on collagen sequences and Helix-II epitope properties, type III collagen is one of several candidate sources of the cross-reacting signal in body fluids, but not type II collagen. The findings highlight the need for more stringent scrutiny of the origins and validation of molecular markers in body fluid assays in general.

摘要

目的

在研究螺旋-II 软骨生物标志物免疫测定的基础序列时,发现了一个明显的数据库错误。

方法和结果

串联质谱确定了人类 II 型胶原中的肽序列 ERGETGPPGPA,而不是用于生成螺旋-II 测定抗体的 ERGETGPPGTS。

结论

最近有报道称,将螺旋-II 测定法应用于尿液或血清作为软骨胶原蛋白降解的标志物,由于该表位不存在于 II 型胶原中,因此需要重新评估。基于胶原序列和螺旋-II 表位特性,III 型胶原是几种候选的体液中交叉反应信号来源之一,但不是 II 型胶原。这些发现强调了需要更严格地审查生物体液检测中分子标志物的来源和验证。

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