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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02938-3

摘要内容如下：

尽管B细胞与多发性硬化症（MS）的病理生理学有关，但预测或诊断自身抗体仍然难以捉摸。在这项研究中，国防部血清库（DODSR），一个超过1000万人的队列，被用来生成数百名多发性硬化症（PWMS）患者发病前和发病后数年的全蛋白质组自身抗体谱。该分析在大约10%的PWM中定义了一个独特的簇，这些PWM共享针对与许多人类病原体相似的共同基序的自身抗体信号。这些患者在出现MS症状前数年就表现出抗体反应性，并且与其他PWM相比具有更高的血清神经丝光（SNFL）水平。此外，随着时间的推移，这一特征被保留下来，为临床发病前数年的免疫活性临床前期提供了分子证据。这种自身抗体反应性在脑脊液和血清中来自单独的偶发MS队列的样本中得到了验证，其中它对最终诊断为MS的患者具有高度特异性。该标记是该MS患者亚群的进一步免疫学表征的起点，并可能在临床上用作患有临床或放射学孤立神经炎症综合征的高危患者的抗原特异性生物标志物。

英文原文如下：

Abstracts

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster in approximately 10% of PwMS who share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS. Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active preclinical period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid and serum, where it is highly specific for patients eventually diagnosed with MS. This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes.

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