Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO)
Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO)
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DOI：
10.1007/s00296-016-3466-7
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Hedrich, Christian Michael
中科院分区：
文献类型：
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作者：
Hofmann, Sigrun Renate;Kubasch, Anne Sophie;Hedrich, Christian Michael
慢性复发性多灶性骨髓炎 (CRMO) 是慢性非细菌性骨髓炎最严重的形式，是一种自身炎症性骨病。由于缺乏广泛接受的诊断标准和不完整的病理生理学理解，及时诊断和治疗变得复杂。本研究的目的是确定用于 CRMO 诊断和随访的生物标志物。诊断时收集了 56 名 CRMO 患者的血清。作为对照，收集了年龄匹配的克罗恩病 (N = 62) 或 JIA (N = 28) 以及健康个体 (N = 62) 的年龄匹配患者的血清。对 25 种炎症标志物进行了多重分析。使用 Kruskal-Wallis 和 Mann-Whitney U 检验、典型判别分析和混合模型方差分析进行统计分析。大多数单核细胞来源的血清蛋白均可检测到，并且组间差异显着：IL-1RA、IL-2R、IL-6、IL-12、eotaxin、MCP-1、MIP-1b、RANTES。多成分判别分析允许定义区分 CRMO、克罗恩病和健康对照的算法。在 CRMO 患者的随访样本中，持续高水平的 MCP-1、IL-12、sIL-2R 与不完全缓解相关。区分算法可以区分 CRMO 或克罗恩病患者与健康个体。 IL-12、MCP-1 和 sIL-2R 可作为治疗反应的标志物。尽管有必要在更大的多种族队列中证实我们的研究结果，但它们可能被证明对于区分健康个体或患有“骨痛”的克罗恩病患者和 CRMO 患者很有价值。主要源自单核细胞的促炎血清蛋白的升高支持了促炎单核细胞/巨噬细胞驱动CRMO炎症的假设。
Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis, is an autoinflammatory bone disorder. A timely diagnosis and treatment initiation is complicated by the absence of widely accepted diagnostic criteria and an incomplete pathophysiological understanding. The aim of this study was to determine biomarkers for the diagnosis and follow-up of CRMO. Serum of 56 CRMO patients was collected at the time of diagnosis. As controls, sera from treatment-na < ve age-matched patients with Crohn's disease (N = 62) or JIA (N = 28) as well as healthy individuals (N = 62) were collected. Multiplex analysis of 25 inflammation markers was performed. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests, canonical discriminant analysis, and mixed model variance analysis. Mostly monocyte-derived serum proteins were detectable and differed significantly between groups: IL-1RA, IL-2R, IL-6, IL-12, eotaxin, MCP-1, MIP-1b, RANTES. Multicomponent discriminant analysis allowed for the definition of algorithms differentiating between CRMO, Crohn's disease, and healthy controls. Persistently high levels of MCP-1, IL-12, sIL-2R correlated with incomplete remission in follow-up samples from CRMO patients. Discrimination algorithms allow differentiation between patients with CRMO or Crohn's disease, and healthy individuals. IL-12, MCP-1, and sIL-2R can act as markers for treatment response. Though confirmation of our findings in larger multiethnical cohorts is warranted, they may prove valuable to differentiate between otherwise healthy individuals or Crohn's disease patients with "bone pain" and CRMO patients. The elevation of mainly monocyte-derived pro-inflammatory serum proteins supports the hypothesis of pro-inflammatory monocyte/macrophages driving inflammation in CRMO.