肌痛性脑脊髓炎/慢性疲劳综合征患者针对 Epstein-Barr 病毒的 IgG 抗体反应:用于疾病诊断和病理性抗原模拟的有效潜力。
IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.
机构信息
Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal.
CEAUL-Centre of Statistics and its Applications, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal.
出版信息
Medicina (Kaunas). 2024 Jan 15;60(1):161. doi: 10.3390/medicina60010161.
The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS.
肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)的诊断和病理学仍存在争议。然而,越来越多的证据表明,EBV 和其他病毒感染引起的 ME/CFS 存在自身免疫成分。在这项工作中,我们分析了一个大型公共数据集,该数据集包含针对 3054 个 EBV 肽的 IgG 抗体,以了解这些免疫反应是否有助于诊断患者并引发病理性自身免疫;我们将健康对照组(HCs)作为比较队列。随后,我们旨在使用针对训练和测试数据集的 85%准确率的超级学习者算法,预测研究参与者的疾病状态。当我们将所有 ME/CFS 患者的数据或具有非传染性或未知疾病诱因的患者亚组的数据与 HCs 的数据进行比较时,我们无法找到一种基于抗体的分类器,该分类器在测试数据集中的准确率能达到我们的要求。然而,我们可以识别出一个由 26 种抗体组成的分类器,该分类器可以以 100%和 90%的准确率分别区分具有传染性疾病诱因的 ME/CFS 患者和 HCs。最后,我们对与这 26 种抗体相关的 EBV 肽进行了生物信息学分析。我们发现,在分类器中选择的抗体的重要性指标与这些抗体识别的人类蛋白与 EBV 肽之间的最大序列同源性之间没有相关性。总之,针对 EBV 的这 26 种抗体在亚组患者中具有有效的疾病诊断潜力。然而,与这些抗体相关的肽不太可能引起自身免疫 B 细胞反应,这可以解释 ME/CFS 的发病机制。