Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS.
Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS.
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DOI：
10.1212/nxi.0000000000000933
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Rothhammer V
中科院分区：
文献类型：
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作者：
Tsaktanis T;Beyer T;Nirschl L;Linnerbauer M;Grummel V;Bussas M;Tjon E;Mühlau M;Korn T;Hemmer B;Quintana FJ;Rothhammer V
血清芳香烃受体(AHR)激动型活性水平与疾病严重程度的关系、其在复发-缓解型MS(RRMS)过程中的调节以及在进展型MS(PMS)中的调节尚不清楚。在这里，我们报告了RRMS和PMS患者横断面和纵向血清样本中AHR激动剂活性水平的分析。在一项横断面调查中，共有36例诊断为非炎症性疾病的对照患者、84例RRMS患者、35例继发性进展性多发性硬化症(SPMS)和41例原发进展性多发性硬化症(PPMS)患者纳入本研究。AHR活性是在基于细胞的荧光素酶分析中测量的，并与年龄、性别、疾病修改疗法的存在、扩展残疾状态量表评分和病程相关。在第二次纵向研究中，我们分析了13名被诊断为RRMS的患者在4年至10年期间的AHR活性，并将AHR活性与脑白质萎缩和病变负荷体积变化联系起来。在RRMS中，AHR配体水平整体下降，并与病程和神经功能障碍相关。在SPMS和PPMS中，血清AHR激动剂活性降低，且与疾病严重程度相关。最后，在RRMS患者的纵向血清样本中，AHR激活性降低与进行性中枢神经系统萎缩和病变负荷增加有关。这些发现表明，血清AHR激动剂水平与RRMS和PMS的残疾程度呈负相关，并与疾病进展的MRI标志物纵向相关。因此，血清AHR激活性可作为MS患者残疾进展的新的生物标志物。
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. 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. 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. 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.