Summary for severe patients:
– London Group found herpes reactivated in saliva
– Herpes are localized infections, just like enteroviruses
– Most patients had high antibody response to the dUTPase protein that herpes viruses use
– Healthy controls had little to no antibody response to dUTPase
– Antibody to dUTPase lower = more severe ME/CFS, possibly suggesting a failed immune reply
– More Antibody response to herpes dUTPase = probably reactivated and insufficient immune response, more moderate or mild MECFS
– This protein then causes mitochondrial fragmentation
– Protein tends to bind to cellular cytoskeleton, which in turn alter mitochondrial structure, suggesting it fragments mitochondria indirectly
– Interestingly, extracellular expression can cause mitochondria fragmentation too
– They looked for 120 auto antigens (IgG and IgM) in an assay
– IgG Autoantibodies did NOT relate to disease severity
– ME/CFS patients have overlapping SLE and MS antibodies
– IgM antibodies DID associate with disease severity
– IgM response in severe patients have IgMs to all sorts of pathogenic stuff like dust, cats, apples, flowers, etc. implying poor complement activation
– IgM response to many things is also significantly DECREASED, as well in ALL patients
– Some of the IgM responses can explain some of the disease symptoms, for example AQ4 (Aquaporin-4) related to light sensitivity in MECFS patients
– AQ4 is a water channel protein involved in neuropathology, specifically the optic nerve, and antibodies to this cause the optic nerve to lose control over water channels, in turn causing light sensitivity
– This is just one example of the IgMs he found in correlation to symptoms
– Immunoglobulins from severe MECFS patients can induce mitochondrial fragmentation in healthy primary endothelial cells and also cause mitochondria to stick together (this could be why MECFS blood is ‘sticky’)
– 3 proteins significantly decreased in ME/CFS: TF (Transferrin), A2M (Alpha-2-macroglobulin), and FN1 (Fibronectin-1)
– Circulating Fibronectin is extremely high in serum/plasma and high in cells, but evidently has low function and is not being incorporated into the complement (immune system) proteins, and we don’t know why yet
– Higher Fibronectin is associated with greater disease severity
– Fibronectin is not the most sensitive biomarker, but interesting nonetheless
– Fibronectin causes pro inflammatory response and a vicious cycle
– Fibronectin binds to TLR4 causing innate immune response
– Fibronectin causes EDS, MCAS, metabolism
– Fibronectin is a secondary disease state, not the causative factor, but something that significantly can impact disease symptoms and severity
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