1/ This excellent study by @aaronmring/@VirusesImmunity and team found that COVID-19 patients exhibit dramatic increases in the production of antibodies against thousands of human extracellular and secreted proteins (the exoproteome) compared to controls 👇
2/ The million dollar question is: what molecular mechanisms underly this antibody/#autoantibody production? It is worth interpreting the findings via the lens of human #microbiome/#virome activity + the activity of persistent pathogens (such as EBV) harbored by study subjects.
3/ Every study subject harbored extensive microbiome/virome communities comprised of trillions of organisms during #COVID-19 infection…with such ecosystems now understood to persist beyond just the gut but also in other body sites (#lung, liver etc).
4/ Nearly all bacterial/viral/fungal members of such communities are #pathobionts: organisms capable of changing their gene expression to act as pathogens under conditions of imbalance/immunosuppression: ncbi.nlm.nih.gov/pmc/articles/P…
5/ This pathobiont activity can lead to increased expression of pathogenic proteins. And the human #immune system often responds to a pathobiont or its proteins by creating #antibodies capable of cross-reacting with human tissue/receptors etc via molecular mimicry.
6/ For example, this @Yale team identified pathobiont E. gallinarum in the mesenteric veins, mesenteric lymph nodes, liver, and spleens of mice made genetically prone to autoimmunity....: science.sciencemag.org/content/359/63… Image
7/....In these mice, E. gallinarum initiated the production of “#autoantibodies,” activated T cells, and #inflammation. However this “autoantibody” production stopped when E. gallinarum’s growth was suppressed with the antibiotic vancomycin.
8/ ...Indeed , anti-dsDNA, anti-RNA autoantibodies, anti-b2GPI immunoglobulin G, hepatic and serum ERV gp70, and anti-ERV gp70 immune complexes were all suppressed by vancomycin treatment.
8/ Or consider this study: the team tested healthy women for the presence of IgG/IgA autoantibodies directed against 14 key regulatory peptides including leptin, ghrelin, vasopressin, and insulin..... pubmed.ncbi.nlm.nih.gov/18262391/ Image
9/ ....Numerous cases of sequence homology were identified between these #peptides and the protein structures of over 30 #microbes including Listeria monocytogenes, E. coli, Lactobacilli, H. pylori etc.
10/ Or this study: B cells infected with Epstein Barr #Virus (EBV) secreted antibodies capable of reacting with dozens of self and non-self antigens including albumin, renin, and thyroglobulin: ashpublications.org/blood/article/… Image
11/ So, is it possible that in #COVID-19 patients, at least some “autoantibody” production may be driven by changes in microbiome/virome pathobiont/#pathogen activity that occur when COVID-19 dysregulates the overall immune response?
12/ Certainly that would help explain the diversity of “autoantibody” responses identified in COVID-19 patients in the original @VirusesImmunity study (“autoantibody” production wld reflect activity of the unique microbiome/virome/pathogens harbored by each study subject).
13/ It would be interesting to create a #database of common human pathobionts/proteins…and screen the “autoantibodies” identified in the  COVID-19 study against this microbiome/virome-derived #proteome/#metabolome for sequence homologies.
14/ For more context on the general molecular mechanisms underlying my thinking, please read my paper “Re-framing the Theory of #Autoimmunity in the Era of the Microbiome: Persistent Pathogens, Autoantibodies, and Molecular Mimicry”: discoverymedicine.com/Amy-D-Proal/20…

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More from @microbeminded2

10 Dec
Important paper 👉 A team in Tokyo took RNA-seq data from the Genomic-#Tissue Expression Project: a public resource created to study tissue-specific gene expression/regulation from 54 tissue types collected from 1000+ healthy individuals at autopsy: bmcbiol.biomedcentral.com/articles/10.11…
2/ They successfully identified 39 viral species in at least one tissue (tissue types included #brain, pituitary, esophagus, thyroid, #heart, breast, lung, kidney, adrenal gland, prostate, #nerve, adipose tissue, blood vessel, ovary, uterus etc)
3/ Viruses identified in the various tissue samples included EBV, HSV-1, Varicella, CMV, HHV6-A/B, HHV-7, HCV, HPV, adeno-associated virus...and 16 RNA #viruses including Respiratory syncytial virus (RSV), Parainfluenza Virus 3..
Read 12 tweets
23 Nov
This is an incredibly important preprint to inform #LongCovid. Among many analyses, the team recruited 4 patients w/ prolonged + recurrent olfactory function loss after #COVID-19 (time from first COVID-19 symptoms to inclusion ranged from 110-196 days): biorxiv.org/content/10.110…
2/ None of these patients had detectable COVID-19 #RNA in nasopharyngeal samples by routine diagnosis (RT-qPCR). However, ALL patients had detectable COVID-19 RNA in samples obtained from their olfactory mucosa (confirmed with aRT-qPCR SYBR technique)
3/ Three of the patients had a high COVID-19 #viral load in the olfactory mucosa. Immunostaining additionally revealed the presence of COVID-19 antigens in 3 out of 4 patients. Based on that and related findings the team concluded...
Read 8 tweets
18 Nov
@jenbrea Hey! So I'm getting to the point where I could write a long paper about potential overlapping connections b/t #Alzheimer's and #MECFS, but I'll summarize a few top trends in this thread! First, I brainstormed often on topic with the late Rob Moir
@jenbrea 2/ Rob’s research (done w/ Rudy Tanzi + Will Eimer at Harvard) forms the core of a potential ongoing paradigm shift in Alzheimer’s - namely that #amyloid beta may be an antimicrobial peptide that forms in response to pathogens in #brain tissue: pubmed.ncbi.nlm.nih.gov/30001512/
@jenbrea 3/ To better understand that research, read this #interview I did with Rob before he passed away last year from glioblastoma. Key to ME/CFS is his work indicates that amyloid may form in response to herpesviruses like HSV1 in the Alzheimer’s brain: microbeminded.com/2017/12/18/int…
Read 14 tweets
27 Oct
This interesting study found that skeletal #muscle cells of #ME/CFS patients showed a decrease in oxidative phosphorylation (a metabolic pathway used by #mitochondria to generate #energy). In simple terms, that caused the cells to have a dysregulated #metabolism.
2/ Not mentioned in the paper, but important to consider, is that most well-studied #viral + bacterial #pathogens “hijack” the metabolism of the cells they infect in a manner that can result in decreased oxidative phosphorylation (or similar changes in cell energy pathways).
3/ In simples terms, these #pathogens “hijack” cell metabolism to “pull” substrates out of the human mitochondrial energy pathways...and use the substrates (lipids, fatty acids, amino acids) for their own #nutritional and replication purposes!
Read 6 tweets
11 Oct
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker Walker hi - I very much disagree that #Borrelia or #EBV are typically ” long gone” in infected patients who develop chronic symptoms.
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker 2/ There is a large body of literature showing that even if such #organisms cannot be found in blood, they can persist in certain tissues or the central #nervous system where they are very hard to identify clinically
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker 3/ This is particularly obvious w/ EBV which is a #herpesvirus. Herpesviruses almost never “clear” after #infection, and symptom resolution is due to the immune system’s ability to contain the #virus in a non-replicating state
Read 10 tweets
30 Sep
Boy is it refreshing to read this thread that takes a close look at two studies being used to rationalize #vitamin D supplementation for #COVID-19. It explains how both studies have so many problems that the findings must be interpreted with great caution
2/ Why do I care? I spent part of my graduate work working on the molecular #biology of the vitamin D system (including how the various “vitamin” D metabolites impact Vitamin D Receptor activity/gene expression)
3/ Far from being simplistic “vitamins”, the various forms of “vitamin” D are actually secosteroid transcriptional activators, w/ 1-25-dihydroxyvitamin D (also called D3) also acting as a hormone
Read 11 tweets

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