Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan; Multiple Sclerosis Center, National Center Hospital, NCNP, Tokyo, Japan.
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Brain Behav Immun. 2021 Jul;95:245-255. doi: 10.1016/j.bbi.2021.03.023. Epub 2021 Mar 29.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by fatigue and post-exertional malaise, accompanied by various signs of neurological and autonomic dysfunction. ME/CFS is often triggered by an infectious episode and associated with an aberrant immune system. Here we report that ME/CFS is a disorder characterized by skewed B cell receptor gene usage. By applying a next-generation sequencing to determine the clone-based IGHV/IGHD/IGHJ repertoires, we revealed a biased usage of several IGHV genes in peripheral blood B cells from ME/CFS patients. Results of receiver operating characteristic (ROC) analysis further indicated a possibility of distinguishing patients from healthy controls, based on the skewed B cell repertoire. Meanwhile, B cell clones using IGHV3-30 and IGHV3-30-3 genes were more frequent in patients with an obvious infection-related episode at onset, and correlated to expression levels of interferon response genes in plasmablasts. Collectively, these results imply that B cell responses in ME/CFS are directed against an infectious agents or priming antigens induced before disease onset.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种使人虚弱的疾病，其特征是疲劳和劳累后不适，伴有各种神经和自主功能障碍的迹象。ME/CFS 通常由感染发作引发，并与异常的免疫系统有关。在这里，我们报告 ME/CFS 是一种以 B 细胞受体基因使用偏向为特征的疾病。通过应用下一代测序来确定基于克隆的 IGHV/IGHD/IGHJ 库，我们揭示了 ME/CFS 患者外周血 B 细胞中几种 IGHV 基因的偏向性使用。接收者操作特征（ROC）分析的结果进一步表明，基于偏向性 B 细胞库，有可能将患者与健康对照区分开来。同时，在发病时明显与感染相关的病例中，使用 IGHV3-30 和 IGHV3-30-3 基因的 B 细胞克隆更为频繁，并且与浆母细胞中干扰素反应基因的表达水平相关。总的来说，这些结果表明，ME/CFS 中的 B 细胞反应针对的是感染性病原体或疾病发作前诱导的原始抗原。
