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新型血清生物标志物与早期多发性硬化症中7特斯拉磁共振成像定义的皮质病变、软脑膜强化及深部灰质体积的关联

Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis.

作者信息

Miclea Andrei, Zurawski Jonathan, Healy Brian C, Saxena Shrishti, Lokhande Hrishikesh, Quattrucci Molly, Chu Renxin, Weiner Howard L, Bakshi Rohit, Chitnis Tanuja

机构信息

Brigham Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA.

Department of Neurology, Harvard Medical School, Boston, MA, 02115, USA.

出版信息

Sci Rep. 2025 Apr 8;15(1):12032. doi: 10.1038/s41598-025-95229-x.

Abstract

Gray matter demyelinating lesions, brain atrophy and meningeal inflammation are hypothesized to be relevant in multiple sclerosis (MS) disease pathogenesis, though their relationship to immune alterations in early MS is not well characterized. This study aims to investigate correlations between the concentrations of 112 serum proteins and 7 Tesla MRI-defined measures of disease severity in patients with early MS. In this analysis, patients with CIS or MS having a 7 Tesla brain MRI and blood sample both within five years of MS diagnosis were included (n = 57). Correlational analysis was adjusted for sex, age, and disease duration. Correlation between serum proteins and MRI-defined cortical and thalamic gray matter lesions, leptomeningeal enhancement (presence and foci number), deep gray matter (DGM) structure volumes, whole brain parenchymal volume and total T2 white matter lesion volume was assessed. In this study, cortical lesions were associated with higher IL-15, TNF-alpha, and BAFF levels, and lower levels of FcRL2. Leptomeningeal enhancement was associated with higher levels of PLXNB3 and lower levels of nCDase and CNTN5. Higher IL-1B levels correlated with lower DGM volume while higher levels of CDH6, SIGLEC9, and HAGH correlated with higher DGM volume. These novel associations between serum immune proteins and 7 T MRI outcomes may have relevance as disease biomarkers in early stages of MS.

摘要

灰质脱髓鞘病变、脑萎缩和脑膜炎症被认为与多发性硬化症(MS)的发病机制相关,尽管它们与早期MS免疫改变之间的关系尚未得到充分描述。本研究旨在调查112种血清蛋白浓度与早期MS患者7特斯拉MRI定义的疾病严重程度指标之间的相关性。在该分析中,纳入了在MS诊断后五年内同时进行了7特斯拉脑部MRI和血液样本检测的临床孤立综合征(CIS)或MS患者(n = 57)。相关性分析对性别、年龄和病程进行了校正。评估了血清蛋白与MRI定义的皮质和丘脑灰质病变、软脑膜强化(存在和病灶数量)、深部灰质(DGM)结构体积、全脑实质体积和总T2白质病变体积之间的相关性。在本研究中,皮质病变与较高的IL-15、TNF-α和BAFF水平以及较低的FcRL2水平相关。软脑膜强化与较高的PLXNB3水平以及较低的nCDase和CNTN5水平相关。较高的IL-1B水平与较低的DGM体积相关,而较高的CDH6、SIGLEC9和HAGH水平与较高的DGM体积相关。血清免疫蛋白与7T MRI结果之间的这些新关联可能作为MS早期阶段的疾病生物标志物具有相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5236/11978968/6acf4e4ecefc/41598_2025_95229_Fig1_HTML.jpg

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