Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Not Due to Anti-mitochondrial Antibodies

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.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

“…In this sense, some authors postulate that we could be facing an autoimmune pathology [ 79 ], at least in some of its forms, opening the possibility for a subgroup of patients (yet to be determined) to a treatment with immunomodulators or immunoadsorption [ 80 ]. However, recent publications did not find an increase in the frequency of autoantibodies, such as NMDA (related to some autoimmune encephalitis) nor LRP4, ACHR, and MuSK (associated with myasthenia gravis) [ 81 ], nor against the mitochondrial membrane [ 82 ]. Larger longitudinal studies are needed to determine the role of much of these antibodies, since they also appear elevated in control samples.…”

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

“…Anti-mitochondrial antibodies in general were negative in ME/CFS/SEID populations. This research suggests that mitochondrial dysfunction in ME/CFS/ SEID patients cannot be explained by the presence of circulating anti-mitochondrial autoantibodies [48].…”

Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

“…Because the research on possible biomedical markers is still highly controversial in the literature, it is difficult to recommend specific assays to be used in diagnosis, as more research and evidence are required. Future research efforts should focus on standardizing methods for metabolomic screening of CFS/ME such that findings can be better compared between studies in the future [ 219 ].…”