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血清白细胞介素-6和CCL11/嗜酸性粒细胞趋化因子可能是诊断慢性非细菌性骨髓炎的合适生物标志物。

Serum Interleukin-6 and CCL11/Eotaxin May Be Suitable Biomarkers for the Diagnosis of Chronic Nonbacterial Osteomyelitis.

作者信息

Hofmann Sigrun Ruth, Böttger Fanny, Range Ursula, Lück Christian, Morbach Henner, Girschick Hermann Joseph, Suttorp Meinolf, Hedrich Christian Michael

机构信息

Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Institute for Medical Informatics and Biometry, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

出版信息

Front Pediatr. 2017 Dec 1;5:256. doi: 10.3389/fped.2017.00256. eCollection 2017.

Abstract

OBJECTIVES

Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis (CNO), is an autoinflammatory bone disorder. In the absence of diagnostic criteria or biomarkers, CNO/CRMO remains a diagnosis of exclusion. The aim of this study was to identify biomarkers for diagnosing multifocal disease (CRMO).

STUDY DESIGN

Sera from 71 pediatric CRMO patients, 11 patients with osteoarticular infections, 62 patients with juvenile idiopathic arthritis (JIA), 7 patients with para-infectious or reactive arthritis, and 43 patients with acute leukemia or lymphoma, as well as 59 healthy individuals were collected. Multiplex analysis of 18 inflammation- and/or bone remodeling-associated serum proteins was performed. Statistical analysis included univariate ANOVA, discriminant analysis, univariate receiver operating characteristic (ROC) analysis, and logistic regression analyses.

RESULTS

For 14 of 18 blood serum proteins, significant differences were determined between CRMO patients, at least one alternative diagnosis, or healthy controls. Multi-component discriminant analysis delivered five biomarkers (IL-6, CCL11/eotaxin, CCL5/RANTES, collagen Iα, sIL-2R) for the diagnosis of CRMO. ROC analysis allowed further reduction to a core set of 2 biomarkers (CCL11/eotaxin, IL-6) that are sufficient to discern between CRMO, healthy controls, and alternative diagnoses.

CONCLUSION

Serum biomarkers CCL11/eotaxin and IL-6 differentiate between patients with CRMO, healthy controls, and alternative diagnoses (leukemia and lymphoma, osteoarticular infections, para-infectious arthritis, and JIA). Easily accessible biomarkers may aid in diagnosing CRMO. Further studies testing biomarkers in larger unrelated cohorts are warranted.

摘要

目的

慢性复发性多灶性骨髓炎(CRMO)是慢性非细菌性骨髓炎(CNO)最严重的形式,是一种自身炎症性骨病。由于缺乏诊断标准或生物标志物,CNO/CRMO仍然是一种排除性诊断。本研究的目的是确定诊断多灶性疾病(CRMO)的生物标志物。

研究设计

收集了71例儿童CRMO患者、11例骨关节感染患者、62例幼年特发性关节炎(JIA)患者、7例感染后或反应性关节炎患者、43例急性白血病或淋巴瘤患者以及59名健康个体的血清。对18种与炎症和/或骨重塑相关的血清蛋白进行了多重分析。统计分析包括单因素方差分析、判别分析、单因素受试者工作特征(ROC)分析和逻辑回归分析。

结果

对于18种血清蛋白中的14种,在CRMO患者、至少一种替代诊断或健康对照之间确定了显著差异。多成分判别分析得出了用于诊断CRMO的5种生物标志物(IL-6、CCL11/嗜酸性粒细胞趋化因子、CCL5/调节激活正常T细胞表达和分泌因子、胶原蛋白Iα、可溶性白细胞介素-2受体)。ROC分析允许进一步缩减为一组核心的2种生物标志物(CCL11/嗜酸性粒细胞趋化因子、IL-6),这足以区分CRMO、健康对照和替代诊断。

结论

血清生物标志物CCL11/嗜酸性粒细胞趋化因子和IL-6可区分CRMO患者、健康对照和替代诊断(白血病和淋巴瘤、骨关节感染、感染后关节炎和JIA)。易于获取的生物标志物可能有助于诊断CRMO。有必要在更大的不相关队列中进行进一步的生物标志物测试研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f1a/5716982/9ae77bb96c60/fped-05-00256-g001.jpg

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