Abstract
Metabolic profiling studies have recently indicated dysfunctional mitochondria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This includes an impaired function of pyruvate dehydrogenase complex (PDC), possibly driven by serum factor(s), which leads to inadequate adenosine triphosphate generation and excessive lactate accumulation. A reminiscent energy blockade is likely to occur in primary biliary cholangitis (PBC), caused by anti-PDC autoantibodies, as recently proposed. PBC is associated with fatigue and post-exertional malaise, also signifying ME/CFS. We herein have investigated whether ME/CFS patients have autoreactive antibodies that could interfere with mitochondrial function. We found that only 1 of 161 examined ME/CFS patients was positive for anti-PDC, while all PBC patients (15/15) presented significant IgM, IgG, and IgA anti-PDC reactivity, as previously shown. None of fibromyalgia patients (0/14), multiple sclerosis patients (0/29), and healthy blood donors (0/44) controls showed reactivities. Anti-mitochondrial autoantibodies (inner and outer membrane) were negative in ME/CFS cohort. Anti-cardiolipin antibody levels in patients did not differ significantly from healthy blood donors. In conclusion, the impaired mitochondrial/metabolic dysfunction, observed in ME/CFS, cannot be explained by presence of circulating autoantibodies against the tested mitochondrial epitopes.
Highlights
Myalgic encephalomyelitis (ME), called chronic fatigue syndrome (CFS), or systemic exertional intolerance disease (SEID), is a common debilitating disease of unknown etiology characterized by post-exertional malaise (PEM), cognitive disturbance, unrefreshing sleep, autonomous nerve dysfunction and other characteristic comorbidities [1, 2]
We analyzed whether dysfunctional energy generation from mitochondria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could be explained by the presence of reactive autoantibodies directed against the pyruvate dehydrogenase complex (PDC) enzyme, in analogy to what has been observed in primary biliary cholangitis (PBC)
In contrast to our hypothesis, ME/CFS samples were negative for autoantibodies against PDC, with the exception of three ME/CFS patients: #43 (A = 1.217 at 1:500); ME/CFS patient #69 (A = 0.406 at 1:500); ME/CFS patient #166 (A = 0.418 at 1:500); and #21, a ME/CFS patient with FM comorbidity (A =1.658 at 1:500) that was found weakly/intermediately positive
Summary
Myalgic encephalomyelitis (ME), called chronic fatigue syndrome (CFS), or systemic exertional intolerance disease (SEID), is a common debilitating disease of unknown etiology characterized by post-exertional malaise (PEM), cognitive disturbance, unrefreshing sleep, autonomous nerve dysfunction and other characteristic comorbidities [1, 2]. The biology of ME/CFS is complex and diverse explanatory models for ME/CFS have been proposed include autoimmunity, chronic infection, energy metabolic defect, imbalance in autonomous nervous system and/or hormones, and psychosomatic dysfunction. Anti-mitochondrial Antibodies in ME/CFS Target structure Autoantigen. Cell nucleus Cytoplasmic membrane Mitochondria Neo-antigens Other targets. 5-hydroxytryptamine [4, 5]. Muscarinic M1 acetylcholine receptor [6] Muscarinic M3/4 acetylcholine receptor ß2 adrenergic receptor [7] μ-opioid receptor, 5-hydroxytryptamine receptor, dopamine receptor D2 [6].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call