血清神经胶质纤维酸性蛋白与多发性硬化症复发活动无关的进展相关联。

Association of serum glial fibrillary acidic protein with progression independent of relapse activity in multiple sclerosis.

机构信息

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.

Department of Neurology, Region Västra Götaland, Sahlgrenska University Hospital, Mölndal, Sweden.

出版信息

J Neurol. 2024 Jul;271(7):4412-4422. doi: 10.1007/s00415-024-12389-y. Epub 2024 Apr 26.

DOI:10.1007/s00415-024-12389-y

PMID:38668889

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11233378/

Abstract

OBJECTIVE

Insidious disability worsening is a common feature in relapsing-remitting multiple sclerosis (RRMS). Many patients experience progression independent of relapse activity (PIRA) despite being treated with high efficacy disease-modifying therapies. We prospectively investigated associations of body-fluid and imaging biomarkers with PIRA.

METHODS

Patients with early RRMS (n = 104) were prospectively included and followed up for 60 months. All patients were newly diagnosed and previously untreated. PIRA was defined using a composite score including the expanded disability status scale, 9-hole peg test, timed 25 foot walk test, and the symbol digit modalities test. Eleven body fluid and imaging biomarkers were determined at baseline and levels of serum neurofilament light (sNfL) and glial fibrillary acidic protein (sGFAP) were also measured annually thereafter. Association of baseline biomarkers with PIRA was investigated in multivariable logistic regression models adjusting for clinical and demographic confounding factors. Longitudinal serum biomarker dynamics were investigated in mixed effects models.

RESULTS

Only sGFAP was significantly higher in PIRA at baseline (median [IQR] 73.9 [60.9-110.1] vs. 60.3 [45.2-79.9], p = 0.01). A cut-off of sGFAP > 65 pg/mL resulted in a sensitivity of 68% and specificity of 61%, to detect patients at higher risk of PIRA. In a multivariable logistic regression, sGFAP > 65 pg/mL was associated with higher odds of developing PIRA (odds ratio 4.3, 95% CI 1.44-12.86, p = 0.009). Repeated measures of sGFAP levels showed that patients with PIRA during follow-up had higher levels of sGFAP along the whole follow-up compared to stable patients (p < 0.001).

CONCLUSION

Determination of sGFAP at baseline and follow-up may be useful in capturing disability accrual independent of relapse activity in early RRMS.

摘要

目的

进行性残疾恶化是复发缓解型多发性硬化症（RRMS）的常见特征。尽管许多患者接受了高效疾病修正治疗，但仍有许多患者出现与复发活动无关的进展（PIRA）。我们前瞻性地研究了体液和影像学生物标志物与 PIRA 的相关性。

方法

前瞻性纳入 104 例早期 RRMS 患者并随访 60 个月。所有患者均为初诊且未经治疗。采用扩展残疾状况量表、9 孔钉测试、定时 25 英尺步行测试和符号数字模态测试的综合评分定义 PIRA。在基线时测定 11 种体液和影像学生物标志物，此后每年测定血清神经丝轻链（sNfL）和胶质纤维酸性蛋白（sGFAP）水平。采用多变量逻辑回归模型，调整临床和人口统计学混杂因素，研究基线生物标志物与 PIRA 的相关性。采用混合效应模型研究血清生物标志物的纵向变化。

结果

仅 PIRA 患者的基线 sGFAP 显著升高（中位数[四分位距]73.9[60.9-110.1]比 60.3[45.2-79.9]，p=0.01）。sGFAP＞65 pg/mL 的截断值可检测出 PIRA 风险较高的患者，其敏感性为 68%，特异性为 61%。在多变量逻辑回归中，sGFAP＞65 pg/mL 与发生 PIRA 的几率较高相关（优势比 4.3，95%可信区间 1.44-12.86，p=0.009）。sGFAP 水平的重复测量显示，随访期间发生 PIRA 的患者的 sGFAP 水平在整个随访期间均高于稳定患者（p＜0.001）。