Maes Michael, Leunis Jean-Claude
Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.
Laboratoire Ategis, Brussels, Belgium.
Neuro Endocrinol Lett. 2014;35(7):577-85.
There is evidence that inflammatory, oxidative and nitrosative stress (IO&NS) pathways participate in the pathophysiology of a subgroup of patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Increased IgM-related autoimmune responses to oxidative specific epitopes (OSEs), including malondialdehyde (MDA), oleic acid and phosphatidyl inositol (Pi), and nitroso-(NO)-adducts, including NO-tryptophan (NOW), NO-arginine and NO-cysteinyl, are frequently observed in ME/CFS. Autoimmune responses in ME/CFS may be driven by increased bacterial translocation as measured by IgM and IgA responses to LPS of gram negative bacteria.
The aim of this study is to examine whether IgM responses to OSEs and NO-adducts are related to a better outcome as measured by the Fibromyalgia and Fatigue Rating Scale (FF). 76 ME/CFS patients with initially abnormal autoimmune responses were treated with care-as-usual, including nutraceuticals with anti-IO&NS effects (NAIOS), such as L-carnitine, coenzyme Q10, taurine + lipoic acid, with or without curcumine + quercitine or N-acetyl-cysteine, zinc + glutamine.
We found that use of these NAIOS was associated with highly significant reductions in initially increased IgM-mediated autoimmune responses to OSEs and NO-adducts. A greater reduction in autoimmune responses to OSEs during intake of these NAIOS was associated with a lower FF score. Reductions in IgM responses to oleic acid, MDA and Pi, but not in any of the NO-adducts, were associated with reductions in severity of illness. These associations remained significant after adjusting for possible effects of increased bacterial translocation (leaky gut).
Our results show that autoimmune responses to OSEs are involved in the pathophysiology of ME/CFS and that these pathways are a new drug target in a subgroup of ME/CFS patients. Although hypernitrosylation and nitrosative stress play a role in ME/CFS, reductions in these pathways are not associated with lowered severity of illness. Randomized controlled trials with NAIOS should be carried out in the subgroup of ME/CFS patients with initially increased autoimmune responses to OSEs.
有证据表明，炎症、氧化和亚硝化应激（IO&NS）途径参与了一小部分肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）患者的病理生理过程。在ME/CFS患者中，经常观察到针对氧化特异性表位（OSEs）的IgM相关自身免疫反应增加，这些表位包括丙二醛（MDA）、油酸和磷脂酰肌醇（Pi），以及亚硝基 - （NO） - 加合物，包括NO - 色氨酸（NOW）、NO - 精氨酸和NO - 半胱氨酸。ME/CFS中的自身免疫反应可能由细菌易位增加所驱动，这可通过对革兰氏阴性菌脂多糖的IgM和IgA反应来衡量。
本研究的目的是检验针对OSEs和NO - 加合物的IgM反应是否与通过纤维肌痛和疲劳评定量表（FF）衡量的更好预后相关。76例最初自身免疫反应异常的ME/CFS患者接受常规护理治疗，包括具有抗IO&NS作用的营养补充剂（NAIOS），如左旋肉碱、辅酶Q10、牛磺酸 + 硫辛酸，加或不加姜黄素 + 槲皮素或N - 乙酰半胱氨酸、锌 + 谷氨酰胺。
我们发现使用这些NAIOS与最初升高的IgM介导的针对OSEs和NO - 加合物的自身免疫反应显著降低相关。在摄入这些NAIOS期间，对OSEs的自身免疫反应降低幅度更大与较低的FF评分相关。对油酸、MDA和Pi的IgM反应降低，但对任何NO - 加合物的反应未降低，与疾病严重程度降低相关。在调整细菌易位增加（肠漏）的可能影响后，这些关联仍然显著。
我们的结果表明，针对OSEs的自身免疫反应参与了ME/CFS的病理生理过程，并且这些途径是一小部分ME/CFS患者的新药物靶点。尽管高亚硝化作用和亚硝化应激在ME/CFS中起作用，但这些途径的减少与疾病严重程度降低无关。应该对最初针对OSEs的自身免疫反应增加的ME/CFS患者亚组进行NAIOS的随机对照试验。
