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Toll 样受体 4 激动剂 MRP8/14 蛋白复合物是全身性幼年特发性关节炎疾病活动的敏感指标,并可预测其复发。

The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.

机构信息

Institute of Immunology, University Hospital Muenster, Muenster, Germany.

出版信息

Ann Rheum Dis. 2012 Jun;71(6):974-80. doi: 10.1136/annrheumdis-2011-200598. Epub 2012 Jan 20.

DOI:10.1136/annrheumdis-2011-200598
PMID:22267331
Abstract

BACKGROUND

Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin.

OBJECTIVE

To test the ability of MRP8/14 serum concentrations to monitor disease activity in patients with SJIA and stratify patients at risk of relapse.

METHODS

Serum concentrations of MRP8/14 in 52 patients with SJIA were determined by a sandwich ELISA. The monitoring of therapeutic regimens targeting interleukin 1 and tumour necrosis factor α, and methotrexate treatment was analysed and diagnostic power to predict flares was tested.

RESULTS

MRP8/14 levels were clearly raised in active disease and decreased significantly in response to successful treatments. Serum concentrations of MRP8/14 increased significantly (p<0.001) (mean±95% CI 12.030±3.090 ng/ml) during disease flares compared with patients with inactive disease (864±86 ng/ml). During clinical remission MRP8/14 serum levels of >740 ng/ml predicted disease flares accurately (sensitivity 92%, specificity 88%). MRP8/14 levels correlated well with clinical disease activity, as assessed by physician's global assessment of disease activity (r=0.62), Childhood Health Assessment Questionnaire (r=0.56), active joint count (r=0.46) and with C-reactive protein (r=0.71) and erythrocyte sedimentation rate (r=0.72) (for all p<0.001).

CONCLUSION

MRP8/14 serum concentrations correlate closely with response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with SJIA. MRP8/14 serum concentrations are the first predictive biomarker indicating subclinical disease activity and stratifying patients at risk of relapse during times of clinically inactive disease.

摘要

背景

髓系细胞相关蛋白 8 和 14 复合物(MRP8/14)血清浓度分析可能是一种新的工具,有助于在不明原因发热的情况下支持全身型幼年特发性关节炎(SJIA)的诊断。

目的

检测 MRP8/14 血清浓度在 SJIA 患者中监测疾病活动度的能力,并对复发风险患者进行分层。

方法

采用夹心酶联免疫吸附试验检测 52 例 SJIA 患者的 MRP8/14 血清浓度。分析针对白细胞介素 1 和肿瘤坏死因子 α 以及甲氨蝶呤治疗的治疗方案的监测,并检测其预测病情加重的诊断能力。

结果

在活动期疾病中,MRP8/14 水平明显升高,经成功治疗后显著降低。与疾病缓解期患者(864±86ng/ml)相比,疾病加重期患者的 MRP8/14 血清浓度显著升高(p<0.001)(均值±95%置信区间 12.030±3.090ng/ml)。在临床缓解期,MRP8/14 血清水平>740ng/ml 能准确预测疾病加重(敏感性 92%,特异性 88%)。MRP8/14 水平与临床疾病活动度密切相关,如医生总体疾病活动度评估(r=0.62)、儿童健康评估问卷(r=0.56)、活跃关节计数(r=0.46)、C 反应蛋白(r=0.71)和红细胞沉降率(r=0.72)(均 p<0.001)。

结论

MRP8/14 血清浓度与药物治疗反应和疾病活动度密切相关,因此可能是监测 SJIA 个体患者抗炎治疗的额外指标。MRP8/14 血清浓度是首个预示亚临床疾病活动度的预测生物标志物,并在临床缓解期对复发风险患者进行分层。

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