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Abstract：
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for the assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a subgroup-specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.
摘要：
肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种以深度疲劳为特征的复杂疾病,劳累后不适（PEM），和神经认知功能障碍。在ME/CFS患者中通常观察到免疫失调和胃肠道症状。尽管影响了大约0.89%的普通人口，潜在的病理生理机制仍然知之甚少。本研究旨在阐明ME/CFS患者免疫特性与肠道屏障功能的关系。ME/CFS患者根据其免疫能力分为两组。在记录了详细的医疗记录之后,收集血清和血浆样品用于通过ELISA评估炎性免疫介质和肠屏障完整性的生物标志物。我们发现免疫缺陷型ME/CFS患者补体蛋白C4a水平降低，提示亚组特异性先天免疫失调。无免疫缺陷的ME/CFS患者表现出粘膜屏障渗漏，如脂多糖结合蛋白（LBP）水平升高所示。根据免疫能力对ME/CFS患者进行分层，可以区分具有不同病理生理模式的两个亚组。该研究强调了在ME/CFS中强调精确患者分层的重要性，特别是在定义合适的治疗策略的背景下。鉴于与ME/CFS相关的巨大健康和社会经济负担，需要紧急关注和研究努力来定义致病治疗方法。
