Autoantibody Correlation Signatures in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Association with Symptom Severity

Abstract

Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. However, the natural AAb network is much more extensive, and has not been previously investigated in these disorders. The enzyme immunoassays ELI-Viscero-Test and ELI-Neuro-Test were used to determine changes in serum content of 33 natural AAb to neural, organ-specific and non-tissue-specific autoantigens (a) in 11 ME/CFS patients with comorbid FM; (b) in 11 ME/CFS patients without FM; (c) in 11 healthy controls. Individual AAb profiles and their correlation with some clinical symptoms were analyzed. Both patients with ME/CFS(−)FM and ME/CFS(+)FM were characterized by more frequent and pronounced deviations in the immunoreactivity to GABA-receptors than healthy controls. Although the level of other natural AAb did not differ between study groups, AAb correlation signatures were altered in patients compared to healthy controls. Both in patients and healthy controls the level of natural AAb to various neural and tissue-specific antigens correlated with the severity of fatigue, bodily pain, depression, anxiety, physical and mental health-related quality of life. Notably, widely different correlation patterns were observed between study groups. Findings from this pilot study provide some evidence that the homeostasis of autoimmune relationships, which are possibly a physiological part of our immune system, may be altered in FM and ME/CFS. The correlation of disease-induced perturbations in individual AAb profiles with some clinical symptoms may arise from the immune system’s ability to reflect qualitative and quantitative changes in antigenic composition of the body.

A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in ME/CFS: Implications for Long COVID

“…Interestingly, Long COVID patients also have reported other dysfunctions, which previously were associated with, including neurologic pain, neurocognitive and psychiatric symptoms, however with no cases of rash, as well as olfactory and gustatory dysfunction [11] (Figure 1). Although the exact aetiology of ME/CFS, neither Long COVID still needs to be determined, evidence to date indicate as post-viral syndromes, being most likely triggered by the infectious agent, such as Epstein Barr Virus [12] and SARS-CoV-2 in Long COVID [13], respectively, also share biological abnormalities, with examples of the cognitive deficits, including impaired attention and information processing speed, dysregulation of the hypothalamic-pituitary (HP) axis, and abnormal immune cytokine profile [14], characterized by high auto-antibodies titres against neural and autonomic targets [15,16] including neurotransmitter receptors against nuclear and membrane structures, such as cardiopin and phospholipids, neurotransmitter receptors (e.g., muscarinic M1 acetylcholine receptor (AChR) and ß1-and ß2-adrenergic receptors (AdR) and M2/3 [17]); as well as and increased levels of proinflammatory mediators, interleukin (IL) IL-1 (IL-1α, IL-1β), IL-4, IL-5, IL-6, and IL-12, TNF-α, IL-10, IL-13, IL-16, INF-γ, and IL-17, IL-17A (but reduced IL-17F) [18][19][20], further linked with severity of after mentioned symptoms [21]. In particularly, metabolic abnormalities along with mitochondrial dysfunction and impaired redox balance [22] characterized by increased oxidative toxicity and lowered antioxidant defenses were associated with the development of symptoms of pain and hyper-sensitivity [23] and severity of neuropsychiatric symptoms in both ME/CFS [18] and Long COVID [24].…”

Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review

“…FM is associated with oxidative stress and mitochondrial, immunological, and cardiovascular autonomic dysfunction [ 17 , 18 , 19 , 20 , 21 ]. Furthermore, recent hypotheses concerning its pathophysiology include the role of inflammation, gut dysbiosis, neuroinflammation, and DNA methylation [ 22 , 23 ].…”

A causal link between autoantibodies and neurological symptoms in long COVID

“…Although the root cause(s) of PAIS remain unclear, a wealth of data supports an autoimmune etiology of PAIS 3,[14][15][16][17][18][19][20][21][22][23] . For example, AABs have been found in ME/CFS [24][25][26] , chronic Lyme disease 27,28 , and LC 3,[14][15][16][17][18][19][20][21][22][23] , some of which target GPCRs and GABA receptors involved in neuronal pathways relevant to neurological symptoms.…”