Autoimmune hypothesis

2021-02-24T12:13:14Z

NaomiDTK:/* Evidence for autoimmunity in ME and CFS */

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==Theory==

The Open Medicine Foundation, with immunologist [[Mark Davis]], and geneticist [[Lars Steinmetz]], is currently investigating the replication of [[T cell|T cells]] in ME, which may indicate an autoimmune disease is present in some ME/CFS patients.<ref name="OMF2018research" /> [[Human leukocyte antigen genes|HLA gene]] associations are a possible hallmark of autoimmune disease, and were investigated by [[Øystein Fluge|Fluge]] et al. in 2020.<ref name="Asgeir2020" />
==Evidence==
ME/CFS can cause a number of [[:Category:Immune signs and symptoms|immune symptoms]] including a [[sore throat]], [[swollen lymph nodes]], and [[flu-like symptoms]].<ref name="ICP2011primer">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref><ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|publisher=American College of Physicians}}</ref>

== Evidence for autoimmunity in ME and CFS ==
[[File:MECFS comorbid autoimmune.jpg|alt=Shows fibromyalgia 30-77% overlap, Hashimoto's thyroiditis 17-20%, POTS 11-40% overlap and family history of autoimmune conditions 18-41% overlap.|thumb|Autoimmune conditions in people with ME/CFS. Source: Sotzny et al (2018), [[EUROMENE]] project.]]
Many people with ME/CFS also have autoimmune conditions such as [[Hashimoto's thyroiditis]], or have a family history of autoimmune diseases.<ref name="Sotzny, 2018" /> [[Postural orthostatic tachycardia syndrome|POTS]], or postural orthostatic tachycardia syndrome, can be initiated or maintained by autoantibodies as well, and POTS is common in people with ME. A number of different immune system abnormalities have been found in some patients with ME/CFS.<ref name="Sotzny, 2018" />

One study found elevated cellular antigens in 83% of [[CFS]] patients.<ref>{{Cite journal|last=von Mikecz|first=A.|last2=Konstantinov|first2=K.|last3=Buchwald|first3=D. S.|author-link3=Dedra Buchwald|last4=Gerace|first4=L.|last5=Tan|first5=E. M.|date=Feb 1997|title=High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/m/pubmed/9041942/|journal=Arthritis and Rheumatism|volume=40|issue=2|pages=295–305|issn=0004-3591|pmid=9041942}}</ref>

Autoimmune disease is one of several illnesses or conditions experienced alongside of [[ME/CFS]].<ref>{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-08-12}}</ref>

Samples from a large cohort (n=268) in Berlin, Germany and a smaller sample of patients treated with [[Rituximab]] (n=25) were measured against controls (n=168). Researchers found that antibodies against a [[neurotransmitter]] receptor were elevated in 29.5% of patients. Specifically, antibodies to ß2 [[Adrenergic receptor|adrenergic]] and M3 and M4 muscarinic cholinergic receptors, which are both G protein-coupled receptors (GCPRs). In patients receiving Rituximab, those who were responders had significantly lower levels of ß2 and M4 autoantibodies after treatment. The authors suggest that these autoantibodies could be [[biomarker]]s to those CFS patients most likely to respond to Rituximab treatment.<ref>{{Cite web|url=https://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/|title=Autoantibodies found in subset of CFS patients {{!}} #MEAction|website=www.meaction.net|language=en-US|access-date=2018-08-12}}</ref><ref>{{Cite journal|last=Loebel|first=Madlen|author-link1=Madlen Löbel|last2=Grabowski|first2=Patricia|author-link2=Patricia Grabowski|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|author-link4=Sandra Bauer|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>

==Notable studies==
*2020, Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts<ref name="Bynke2020">{{Cite journal|last=Bynke|first=Annie|author-link=|last2=Julin|first2=Per|author-link2=|last3=Gottfries|first3=Carl-Gerhard|author-link3=Carl-Gerhard Gottfries|last4=Heidecke|first4=Harald|author-link4=|last5=Scheibenbogen|first5=Carmen|author-link5=Carmen Scheibenbogen|last6=Bergquist|first6=Jonas|author-link6=Jonas Bergquist|date=2020-08-01|title=Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts|url=http://www.sciencedirect.com/science/article/pii/S2666354620300727|journal=Brain, Behavior, & Immunity - Health|language=en|volume=7|issue=|pages=100107|doi=10.1016/j.bbih.2020.100107|issn=2666-3546|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [http://www.sciencedirect.com/science/article/pii/S2666354620300727 (Full text)]
*2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="Asgeir2020">{{Cite journal|last=Lande|first=Asgeir|author-link=Asgeir Lande|last2=Fluge|first2=Øystein|author-link2=Øystein Fluge|last3=Strand|first3=Elin B.|author-link3=Elin Strand|last4=Flåm|first4=Siri T.|author-link4=Siri Flåm|last5=Sosa|first5=Daysi D.|author-link5=Daysi Sosa|last6=Mella|first6=Olav|author-link6=Olav Mella|last7=Egeland|first7=Torstein|author-link7=|last8=Saugstad|first8=Ola D.|author-link8=|last9=Lie|first9=Benedicte A.|author-link9=|date=2020-03-24|title=Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.nature.com/articles/s41598-020-62157-x|journal=Scientific Reports|language=en|volume=10|issue=1|pages=1–8|doi=10.1038/s41598-020-62157-x|issn=2045-2322|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-020-62157-x (Full text)]
*2018, Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model<ref name="Blomberg2018">{{Cite journal|last=Blomberg|first=Jonas|author-link=Jonas Blomberg|last2=Gottfries|first2=Carl-Gerhard|author-link2=Carl-Gerhard Gottfries|last3=Elfaitouri|first3=Amal|author-link3=|last4=Rizwan|first4=Muhammad|author-link4=|last5=Rosén|first5=Anders|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2018-02-15|title=Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818468/|journal=Frontiers in Immunology|volume=9|issue=|pages=|doi=10.3389/fimmu.2018.00229|issn=1664-3224|pmc=5818468|pmid=29497420|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818468/ (Full text)]
*2018, [http://10.1016/j.autrev.2018.01.009 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease]<ref name="Sotzny, 2018">{{citation | last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 = Sophie Steiner
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = 17 | issue = 6 | page = 601-609 | date = 2018 | doi = 10.1016/j.autrev.2018.01.009
}}</ref>
*2017-2020, Defining Autoimmune Aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="2017trial">{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT03254823|title=Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - Full Text View|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=clinicaltrials.gov|language=en|archive-url=|archive-date=|dead-url=|access-date=2020-04-25}}</ref> - [https://clinicaltrials.gov/ct2/show/NCT03254823 Clinical Trial]
*2014, [http://www.ncbi.nlm.nih.gov/m/pubmed/24068616/?i=3 The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)]<ref name="Morris2014">{{Cite journal|last=Morris|first=Gerwyn|author-link=Gerwyn Morris|last2=Berk|first2=Michael|author-link2=Michael Berk|last3=Galecki|first3=Piotr|author-link3=Piotr Galecki|last4=Maes|first4=Michael|author-link4=Michael Maes|author-link5=|author-link6=|date=2014-04-01|title=The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/cfs)|url=https://doi.org/10.1007/s12035-013-8553-0|journal=Molecular Neurobiology|language=en|volume=49|issue=2|pages=741–756|doi=10.1007/s12035-013-8553-0|issn=1559-1182|quote=|via=}}</ref>
*2013, [http://www.ncbi.nlm.nih.gov/m/pubmed/23664637/ In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation]<ref name="Maes2013">{{Cite journal|last=Maes|first=Michael|author-link=Michael Maes|last2=Ringel|first2=Karl|author-link2=Karl Ringel|last3=Kubera|first3=Marta|author-link3=Marta Kubera|last4=Anderson|first4=George|author-link4=George Anderson|last5=Morris|first5=Gerwyn|author-link5=Gerwyn Morris|last6=Galecki|first6=Piotr|author-link6=Piotr Galecki|last7=Geffard|first7=Michel|author-link7=Michel Geffard|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=http://www.sciencedirect.com/science/article/pii/S0165032713002541|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=0165-0327|quote=|via=}}</ref>
*2012, [http://www.ncbi.nlm.nih.gov/m/pubmed/22166399/ Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression]<ref name="Maes2012">{{Cite journal|last=Maes|first=Michael|author-link=Michael Maes|last2=Ringel|first2=Karl|author-link2=Karl Ringel|last3=Kubera|first3=Marta|author-link3=Marta Kubera|last4=Berk|first4=Michael|author-link4=Michael Berk|last5=Rybakowski|first5=Janusz Rybakowski|author-link5=Janusz|author-link6=|date=2012-02-01|title=Increased autoimmune activity against 5-HT : a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression|url=http://dro.deakin.edu.au/view/DU:30047500|journal=Journal of affective disorders|volume=136|issue=3|pages=386–392|doi=10.1016/j.jad.2011.11.016|issn=0165-0327|quote=|via=}}</ref>
*2004, [http://www.ncbi.nlm.nih.gov/m/pubmed/15082083 Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?]<ref name="Staines2004">{{Cite journal|last=Staines|first=Donald R|author-link=Donald Staines|author-link2=|author-link3=|author-link4=|author-link5=|author-link6=|date=2004-05-01|title=Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?|url=http://www.sciencedirect.com/science/article/pii/S0306987704000659|journal=Medical Hypotheses|volume=62|issue=5|pages=646–652|doi=10.1016/j.mehy.2004.01.012|issn=0306-9877|quote=|via=}}</ref> - [[Donald Staines]]

==Talks and interviews==
*2015, [https://www.youtube.com/watch?v=FWbC08cbP30 Partnerships to Accelerate Biomarker and Mechanisms Discovery in ME/CFS and Fibromyalgia] - Professor [[Alan Light]] discusses recent studies hypothesising autoimmune causation)

==See also==
*[[Autoimmune disease]]
*[[Innate immune system]]
*[[Rituximab]]
*[[Cyclophosphamide]]
*[[Autoantibody]]
*[[Human leukocyte antigen genes]] (HLA genes)

==Learn more==
*[https://www.omf.ngo/2018/02/28/omf-funded-research-t-cells-molecular-immunology/ T-cells, molecular Immunology and autoimmune hypothesis]<ref name="OMF2018research">{{Cite web|url=https://www.omf.ngo/2018/02/28/omf-funded-research-t-cells-molecular-immunology/|title=OMF-funded research: T cells and molecular immunology|last=Open Medicine Foundation|first=|authorlink=Open Medicine Foundation|last2=|first2=|authorlink2=|date=Feb 28, 2018|website=Open Medicine Foundation|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-07-11}}</ref> - [[Open Medicine Foundation]]
*[https://autoimmune-encephalitis.org/diagnosis/ Autoimmune encephalitis - diagnosis] - International Autoimmune Encephalitis Society
*[https://rarediseases.info.nih.gov/diseases/11979/autoimmune-encephalitis Autoimmune encephalitis] - Genetic and Rare Diseases Information Center

==References==
<references />

[[Category:Medical hypotheses]]
[[Category:Immunology]]

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Autoimmune hypothesis