芳基烃受体血浆激动剂活性与进行性 MS 疾病活动相关。
Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS.
机构信息
From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2020 Dec 24;8(2). doi: 10.1212/NXI.0000000000000933. Print 2021 Mar.
OBJECTIVE
The relationship between serum aryl hydrocarbon receptor (AHR) agonistic activity levels with disease severity, its modulation over the course of relapsing-remitting MS (RRMS), and its regulation in progressive MS (PMS) are unknown. Here, we report the analysis of AHR agonistic activity levels in cross-sectional and longitudinal serum samples of patients with RRMS and PMS.
METHODS
In a cross-sectional investigation, a total of 36 control patients diagnosed with noninflammatory diseases, 84 patients with RRMS, 35 patients with secondary progressive MS (SPMS), and 41 patients with primary progressive MS (PPMS) were included in this study. AHR activity was measured in a cell-based luciferase assay and correlated with age, sex, the presence of disease-modifying therapies, Expanded Disability Status Scale scores, and disease duration. In a second longitudinal investigation, we analyzed AHR activity in 13 patients diagnosed with RRMS over a period from 4 to 10 years and correlated AHR agonistic activity with white matter atrophy and lesion load volume changes.
RESULTS
In RRMS, AHR ligand levels were globally decreased and associated with disease duration and neurologic disability. In SPMS and PPMS, serum AHR agonistic activity was decreased and correlated with disease severity. Finally, in longitudinal serum samples of patients with RRMS, decreased AHR agonistic activity was linked to progressive CNS atrophy and increased lesion load.
CONCLUSIONS
These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS.
目的
血清芳香烃受体（AHR）激动活性水平与疾病严重程度之间的关系、其在复发性缓解型多发性硬化症（RRMS）病程中的变化及其在进展型多发性硬化症（PMS）中的调节尚不清楚。本研究报告了对 RRMS 和 PMS 患者横断面和纵向血清样本中 AHR 激动活性水平的分析。
方法
在横断面研究中，共纳入 36 名诊断为非炎症性疾病的对照患者、84 名 RRMS 患者、35 名继发进展型 MS（SPMS）患者和 41 名原发进展型 MS（PPMS）患者。采用基于细胞的荧光素酶测定法测量 AHR 活性，并将其与年龄、性别、疾病修正治疗的存在、扩展残疾状态量表评分和疾病持续时间相关联。在第二项纵向研究中，我们分析了 13 名 RRMS 患者在 4 至 10 年内的 AHR 活性，并将 AHR 激动活性与白质萎缩和病变负荷体积变化相关联。
结果
RRMS 患者的 AHR 配体水平普遍降低，并与疾病持续时间和神经功能障碍相关。SPMS 和 PPMS 患者血清 AHR 激动活性降低，与疾病严重程度相关。最后，在 RRMS 患者的纵向血清样本中，AHR 激动活性降低与进行性中枢神经系统萎缩和病变负荷增加相关。
结论
这些发现表明，RRMS 和 PMS 患者的血清 AHR 激动剂水平与残疾呈负相关，并且与 MRI 疾病进展标志物呈纵向下降相关。因此，血清 AHR 激动活性可能是 MS 残疾进展的新型生物标志物。
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