滑液中的 LTF、PRTN3 和 MNDA 作为假体周围关节感染的有前途的生物标志物：四极轨道阱质谱法的鉴定。

LTF, PRTN3, and MNDA in Synovial Fluid as Promising Biomarkers for Periprosthetic Joint Infection: Identification by Quadrupole Orbital-Trap Mass Spectrometry.

机构信息

Departments of Clinical Laboratory Medicine (Chi Wang, Q.W., Q.Z., and Chengbin Wang) and Orthopedics (Q.W., R.L., and J.C.), People's Liberation Army General Hospital, Beijing, People's Republic of China.

State Key Laboratory of Proteomics, National Center for Protein Sciences (The PHOENIX Center), Beijing Proteome Research Center, Beijing, People's Republic of China.

出版信息

J Bone Joint Surg Am. 2019 Dec 18;101(24):2226-2234. doi: 10.2106/JBJS.18.01483.

DOI:10.2106/JBJS.18.01483

PMID:31644522

Abstract

BACKGROUND

Diagnosing periprosthetic joint infection (PJI) requires various laboratory and clinical criteria. The purpose of this study was to explore novel biomarkers that could rapidly diagnose PJI with high accuracy.

METHODS

In this retrospective study of prospectively collected samples, 50 synovial fluid aspirates, 20 from the hip and 30 from the knee, were collected before surgery; 25 of the patients were diagnosed as having aseptic loosening (non-PJI) and 25, as having PJI according to the Musculoskeletal Infection Society criteria. A quadrupole orbital-trap mass spectrometry (MS) instrument was used to compare expression of proteins in patients with and without PJI. Proteins that were most efficacious for diagnosis of PJI were then determined using prediction analysis of microarray software and a random forest model. The most promising proteins were selected, and altered expression of these selected proteins was verified by ELISA (enzyme-linked immunosorbent assay) in an extended sample cohort.

RESULTS

A total of 256 proteins were significantly upregulated (≥3.0-fold) and 14 proteins were downregulated in synovial fluid of patients with PJI compared with patients without PJI. The 3 most promising proteins were lactoferrin (LTF), polymorphonuclear leukocyte serine protease 3 (PRTN3), and myeloid nuclear differentiation antigen (MNDA). When MS was used for diagnosis of PJI, the area under the curve was 0.9888 for LTF, 0.9488 for PRTN3, and 0.9632 for MNDA. ELISA results verified that LTF, MNDA, and PRTN3 were sensitive, while LTF and MNDA were specific, for diagnosis of PJI.

CONCLUSIONS

This proteomic study identified a previously noted protein and 2 novel candidate proteins as promising synovial fluid biomarkers for PJI diagnosis, and they should be further validated in future clinical trials.

LEVEL OF EVIDENCE

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

摘要

背景

诊断人工关节假体周围感染（PJI）需要各种实验室和临床标准。本研究旨在探索能够快速、准确诊断 PJI 的新型生物标志物。

方法

在这项前瞻性采集样本的回顾性研究中，共采集了 50 例关节滑液抽吸物，其中 20 例来自髋关节，30 例来自膝关节。在术前采集；25 例患者被诊断为无菌性松动（非 PJI），25 例根据肌肉骨骼感染协会标准被诊断为 PJI。使用四极轨道阱质谱（MS）仪比较 PJI 患者和非 PJI 患者的蛋白质表达。然后使用预测分析微阵列软件和随机森林模型确定对 PJI 诊断最有效的蛋白质。选择最有前途的蛋白质，并通过 ELISA（酶联免疫吸附试验）在扩展样本队列中验证这些选定蛋白质的表达变化。

结果

与非 PJI 患者相比，PJI 患者的关节滑液中有 256 种蛋白质显著上调（≥3.0 倍），14 种蛋白质下调。最有前途的 3 种蛋白质是乳铁蛋白（LTF）、多形核白细胞丝氨酸蛋白酶 3（PRTN3）和髓系核分化抗原（MNDA）。当 MS 用于诊断 PJI 时，LTF 的曲线下面积为 0.9888，PRTN3 为 0.9488，MNDA 为 0.9632。ELISA 结果验证了 LTF、MNDA 和 PRTN3 对 PJI 的诊断具有敏感性，而 LTF 和 MNDA 对 PJI 的诊断具有特异性。