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慢性炎症性脱髓鞘性多发性神经病及其变异型中的钙卫蛋白——一种疾病活动的潜在新型生物标志物

Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants-A Potential Novel Biomarker of Disease Activity.

作者信息

Stascheit Frauke, Hotter Benjamin, Klose Sarah, Meisel Christian, Meisel Andreas, Klehmet Juliane

机构信息

Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

出版信息

Front Neurol. 2021 Sep 13;12:723009. doi: 10.3389/fneur.2021.723009. eCollection 2021.

Abstract

In chronic inflammatory demyelinating polyneuropathy (CIDP), there is an urgent need for biomarkers to monitor ongoing disease activity. Serum calprotectin (CLP) induces signaling pathways involved in inflammatory processes and has been shown to correlate with markers of disease activity in other autoimmune disorders. Thus, we wanted to study the potential value of CLP in comparison to serum neurofilament light chain (sNfl) to monitor disease activity. Sera from 63 typical and atypical CIDP and 6 MMN patients with varying degrees of disease activity were analyzed in comparison with 40 healthy controls (HC) in a cross-sectional design. Association of CLP and sNfl levels with socio-demographics, disease duration, CIDP disease activity scale (CDAS), and impairment status [medical research council-sum score (MRC-SS), the inflammatory neuropathy cause and treatment disability score (INCAT-DS), grip strength, and maximum walking distance], patient-reported outcome (PRO) parameters [SF-36 questionnaire, Beck's depression index (BDI), and fatigue severity scale (FSS)], as well as treatment regime were investigated using uni- and multivariate analysis. CLP and sNfl levels were significantly higher in all CIDP patients compared to HC ( = 0.0009). Multivariate analysis adjusted for age and gender revealed that CLP acts as an independent predictor for CIDP and MMN. CLP was significantly associated with active disease course according to CDAS and correlated with MRC-SS, whereas sNfl correlated with parameters of disease impairment. There was no correlation with PRO, except for sNfl and the mental health composite score. Subgroup analysis revealed no differences between typical CIDP and atypical variants. CLP was elevated in CIDP and variants and was associated with active disease course, whereas sNfl shows further potential as biomarker of axonal degeneration. Thus, CLP might be a suitable additive biomarker for measurement of ongoing inflammation, which is greatly needed to guide better patient care in CIDP.

摘要

在慢性炎症性脱髓鞘性多发性神经病(CIDP)中,迫切需要生物标志物来监测疾病的持续活动。血清钙卫蛋白(CLP)可诱导参与炎症过程的信号通路,并且已证明其与其他自身免疫性疾病中的疾病活动标志物相关。因此,我们希望研究CLP与血清神经丝轻链(sNfl)相比在监测疾病活动方面的潜在价值。采用横断面设计,对63例典型和非典型CIDP患者以及6例疾病活动程度不同的多灶性运动神经病(MMN)患者的血清与40名健康对照(HC)进行了分析。使用单变量和多变量分析研究了CLP和sNfl水平与社会人口统计学、疾病持续时间、CIDP疾病活动量表(CDAS)以及损伤状态[医学研究委员会总分(MRC-SS)、炎性神经病病因及治疗残疾评分(INCAT-DS)、握力和最大步行距离]、患者报告结局(PRO)参数[SF-36问卷、贝克抑郁指数(BDI)和疲劳严重程度量表(FSS)]以及治疗方案之间的关联。与HC相比,所有CIDP患者的CLP和sNfl水平均显著更高(P = 0.0009)。根据年龄和性别进行校正的多变量分析显示,CLP是CIDP和MMN的独立预测因子。根据CDAS,CLP与疾病活动期显著相关,且与MRC-SS相关,而sNfl与疾病损伤参数相关。除了sNfl与心理健康综合评分外,与PRO均无相关性。亚组分析显示典型CIDP和非典型变体之间无差异。CLP在CIDP及其变体中升高,且与疾病活动期相关,而sNfl作为轴突变性的生物标志物具有更大潜力。因此,CLP可能是用于测量持续炎症的合适的附加生物标志物,这对于指导CIDP患者获得更好的治疗非常必要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f7/8473624/ed0437e66bc2/fneur-12-723009-g0001.jpg

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