Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
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DOI：
10.1111/hae.13196
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发表时间：
2017-07-01
期刊：
影响因子：
3.9
通讯作者：
Manon-Jensen, T.
中科院分区：
文献类型：
--
作者：
Hua, B.;Olsen, E. H. N.;Manon-Jensen, T.
简介：进行性关节病引起的关节出血复发是一个严重的并发症haemophili.Aim：我们调查是否软骨和骨降解，炎症的生物标志物改变血友病患者和这些生物标志物是否可以识别血友病患者与arthropathy.Methods：血清35血友病患者不同程度的关节病和43年龄和性别匹配的对照组进行了分析。通过ELISA测量软骨降解（C2M、COMP、CTX-II、ADAMTS 5）、软骨形成（PRO-C2）、骨形成（PINP）、骨吸收（CTX-I）和炎症（hsCRP、CRPM）的生物标志物。通过放射学评估（Pettersson评分）和体格检查（吉尔伯特评分）评估关节病。结果：与对照组相比，血友病患者的C2 M、CTX-II和COMP测量的软骨退化增加了25%（P < 0.05）。软骨降解酶ADAMTS 5的水平在血友病患者中低10%（P < 0.05）。血友病患者骨形成（PINP）减少25%（P < 0.05），而骨吸收（CTX-I）增加30%（P < 0.001）。急性炎症（hsCRP）升高50%（P < 0.01），而慢性炎症（CRPM）降低25%（P < 0.0001）。血友病患者hsCRP/CRPM比值比对照组高60%（P < 0.001）。结合C2M、CRPM和ADAMTS 5的生物标志物组可以区分血友病患者和对照受试者，准确率为85.3%（P < 0.0001）。我们发现没有很强的相关性之间的生物标志物和放射学和物理examination of the joint.Conclusion：生物标志物检测增加软骨和骨降解，并改变血友病关节病患者的炎症活动。这些生物标志物可能用于识别患有进展性关节疾病的患者。
Introduction: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.Aim: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy.Methods: Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score).Results: In patients with haemophilia, cartilage degradation, measured by C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in haemophilia patients (P < 0.05). Bone formation (PINP) was reduced by 25% (P < 0.05) in haemophilia patients, whereas bone resorption (CTX-I) was increased by 30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01), whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophilia patients relative to control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could distinguish haemophilia patients from control subjects with 85.3% accuracy (P < 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint.Conclusion: Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophilia patients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.