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== Autoantibodies found in ME/CFS and its comorbid conditions of POTS and OH == Various studies have detected autoantibodies in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as well as in its common comorbid conditions of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). The table below lists the autoantibodies found in ME/CFS, POTS and OH. {| class="wikitable" |+Autoantibodies Found in ME/CFS, POTS and OH !Autoantibody target !ME/CFS !POTS !OH |- |'''Neurotransmitter receptors''' | | | |- |[[Adrenergic receptor]] alpha 1 | |Yes<ref name=":0">{{Cite journal | last = Li | first = Hongliang | last2 = Yu | first2 = Xichun | last3 = Liles | first3 = Campbell | last4 = Khan | first4 = Muneer | last5 = Vanderlinde-Wood | first5 = Megan | last6 = Galloway | first6 = Allison | last7 = Zillner | first7 = Caitlin | last8 = Benbrook | first8 = Alexandria | last9 = Reim | first9 = Sean | date = 2014-02-26 | title = Autoimmune basis for postural tachycardia syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/24572257 | journal = Journal of the American Heart Association | volume = 3 | issue = 1| pages = e000755|doi=10.1161/JAHA.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref> | |- |[[Adrenergic receptor]] alpha 2 | | | |- |[[Adrenergic receptor]] beta 1 | |Yes<ref name=":0" /> |Yes<ref name=":1">{{Cite journal | last = Yu | first = Xichun | last2 = Stavrakis | first2 = Stavros | last3 = Hill | first3 = Michael A. | last4 = Huang | first4 = Shijun | last5 = Reim | first5 = Sean | last6 = Li | first6 = Hongliang | last7 = Khan | first7 = Muneer | last8 = Hamlett | first8 = Sean | last9 = Cunningham | first9 = Madeleine W. | date = Jan 2012 | title = Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension | url =https://www.ncbi.nlm.nih.gov/pubmed/22130180 | journal = Journal of the American Society of Hypertension: JASH | volume = 6 | issue = 1 | pages = 40–47|doi=10.1016/j.jash.2011.10.003|issn=1878-7436|pmc=3259269|pmid=22130180}}</ref> |- |[[Adrenergic receptor]] beta 2 |Elevated<ref name=":2">{{Cite journal | last = Loebel | first = Madlen | last2 = Grabowski | first2 = Patricia | last3 = Heidecke | first3 = Harald | last4 = Bauer | first4 = Sandra | 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> |Yes<ref name=":0" /> |Yes<ref name=":1" /> |- |Mu-opioid receptor |15% (9 of 60), 0 of 30 controls<ref name=":3" /> | | |- |Dopamine receptor D2 |5% (3 of 60), 0 of 30 controls<ref name=":3" /> | | |- |Serotonin 5-HT1A receptor |Found in 1.7% of patients<ref name=":3" /> | | |- |Muscarinic acetylcholine receptor M1 |53% (32 of 60), 0 of 30 controls<ref name=":3">{{Cite journal | last = Tanaka | first = Susumu | last2 = Kuratsune | first2 = Hirohiko | last3 = Hidaka | first3 = Yoh | last4 = Hakariya | first4 = Yukiko | last5 = Tatsumi | first5 = Ke-Ita | last6 = Takano | first6 = Toru | last7 = Kanakura | first7 = Yuzuru | last8 = Amino | first8 = Nobuyuki | date = Aug 2003 | title = Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/12851722 | journal = International Journal of Molecular Medicine | volume = 12 | issue = 2 | pages = 225–230|issn=1107-3756|pmid=12851722}}</ref> |Yes<ref name=":5">{{Cite web | url = http://www.dysautonomiainternational.org/pdf/Vernino_Muscarinic_Abstract.pdf | title=M1and M2 Muscarinic receptor antibodies among patients with Postural Orthostatic Tachycardia Syndrome: potential disease biomarker | last = Dubey | first = Divyanshu | last2 = Hopkins | first2 = Steve | date = | website = | archive-url = | archive-date = |url-status = | access-date= | last3 = Vernino | first3 = Steven}}</ref> | |- |Muscarinic acetylcholine receptor M2 | |Yes<ref name=":5" /> |Yes<ref name=":1" /> |- |Muscarinic acetylcholine receptor M3 |Elevated<ref name=":2" /> | |Yes<ref name=":1" /> |- |Muscarinic acetylcholine receptor M4 |Elevated<ref name=":2" /> | | |- |Nicotinic ganglionic acetylcholine receptor alpha 3 | |Yes<ref name=":6">{{Cite journal | last = Watari | first = Mari | last2 = Nakane | first2 = Shunya | last3 = Mukaino | first3 = Akihiro | last4 = Nakajima | first4 = Makoto | last5 = Mori | first5 = Yukiko | last6 = Maeda | first6 = Yasuhiro | last7 = Masuda | first7 = Teruaki | last8 = Takamatsu | first8 = Koutaro | last9 = Kouzaki | first9 = Yanosuke | date = 2018-02-28 | title = Autoimmune postural orthostatic tachycardia syndrome | url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899914/ | journal = Annals of Clinical and Translational Neurology | volume = 5 | issue = 4 | pages = 486–492|doi=10.1002/acn3.524|issn=2328-9503|pmc=5899914|pmid=29687025}}</ref> | |- |Nicotinic ganglionic acetylcholine receptor beta 4 | |Yes<ref name=":6" /> | |- |Angiotensin II type 1 receptor | |Yes<ref>{{Cite journal | last = Yu | first = Xichun | last2 = Li | first2 = Hongliang | last3 = Murphy | first3 = Taylor A. | last4 = Nuss | first4 = Zachary | last5 = Liles | first5 = Jonathan | last6 = Liles | first6 = Campbell | last7 = Aston | first7 = Christopher E. | last8 = Raj | first8 = Satish R. | last9 = Fedorowski | first9 = Artur | date = 2018-04-04 | title = Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/29618472 | journal = Journal of the American Heart Association | volume = 7 | issue = 8|doi=10.1161/JAHA.117.008351|issn=2047-9980|pmc=|pmid=29618472}}</ref> | |- |'''Neurotransmitters''' | | | |- |[[Serotonin]] or [[5-hydroxytryptamine]] (5-HT) |62% (26 of 42)<ref name=":4">{{Cite journal | last = Klein | first = R. | last2 = Berg | first2 = P.A. | date = 1995-10-16 | title = High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders |url =https://www.ncbi.nlm.nih.gov/pubmed/9392689 | journal = European Journal of Medical Research | volume = 1 | issue = 1 | pages = 21–26|issn=0949-2321|pmid=9392689}}</ref> 61.5% (72 of 117) ME/CFS, 14% (6 of 43) "chronic fatigue", 6% (2 of 35) controls<ref>{{Cite journal | last = Maes | first = Michael | last2 = Ringel | first2 = Karl | last3 = Kubera | first3 = Marta | last4 = Anderson | first4 = George | last5 = Morris | first5 = Gerwyn | last6 = Galecki | first6 = Piotr | last7 = Geffard | first7 = Michel | 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 =https://pubmed.ncbi.nlm.nih.gov/23664637/ | journal = Journal of Affective Disorders | volume = 150 | issue = 2 | pages = 223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref> | | |- |'''Nuclear envelope autoantibodies''' | | | |- |Lamin B1 (intermediate filament) |52% (31 of 60) nuclear envelope antigens, mostly Lamin B1<ref name=":11" /> | | |- |Cytoplasmic proteins (intermediate filament) |52% (31 of 60) nuclear envelope antigens, some cytoplasmic proteins<ref name=":11" /> | | |- |'''Cytoplasmic membrane antibodies''' | | | |- |[[:Category:Phospholipids|Phospholipids]] (All) |38% (16 of 42)<ref name=":4" /> | | |- |Cardiolipin |95% (38 of 40)<ref>{{Cite journal | last = Hokama | first = Yoshitsugi | last2 = Campora | first2 = Cara Empey | last3 = Hara | first3 = Cynthia | last4 = Kuribayashi | first4 = Tina | last5 = Le Huynh | first5 = Diana | last6 = Yabusaki | first6 = Kenichi | date = 2009 | title = Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/19623655 | journal = Journal of Clinical Laboratory Analysis | volume = 23 | issue = 4 | pages = 210–212|doi=10.1002/jcla.20325|issn=1098-2825|pmid=19623655}}</ref><ref>{{Cite journal | last = Hokama | first = Yoshitsugi | last2 = Empey‐Campora | first2 = Cara | last3 = Hara | first3 = Cynthia | last4 = Higa | first4 = Nicole | last5 = Siu | first5 = Nathaniel | last6 = Lau | first6 = Rachael | last7 = Kuribayashi | first7 = Tina | last8 = Yabusaki | first8 = Kenichi | date = 2008 | title = Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins |url =https://onlinelibrary.wiley.com/doi/abs/10.1002/jcla.20217 | journal = Journal of Clinical Laboratory Analysis|language=en | volume = 22 | issue = 2 | pages = 99–105|doi=10.1002/jcla.20217|issn=1098-2825|pmc = 6649096|pmid=18348309}}</ref> | | |- |β2 glycoprotein | | | |- |[[Phosphatidylinositol]] (PI) |<ref>{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivanka | last3 = Leunis | first3 = Jean-Claude | date = Dec 2007 | title = Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression | url =https://pubmed.ncbi.nlm.nih.gov/18063934/ | journal = Neuro Endocrinology Letters | volume = 28 | issue = 6 | pages = 861–867|issn=0172-780X|pmid=18063934}}</ref> | | |- |Gangliosides |43% (18 of 42)<ref name=":4" /> | | |- |'''Antinuclear autoantibodies (ANA)''' | | | |- |ANA (All) |56.7% (34 of 60)<ref name=":3" /> 68% (41 of 60); 15% controls<ref name=":11">{{Cite journal | last = Konstantinov | first = K | last2 = von Mikecz | first2 = A | last3 = Buchwald | first3 = D | last4 = Jones | first4 = J | last5 = Gerace | first5 = L | last6 = Tan | first6 = E M | date = 1996-10-15 | title = Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome. | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/ | journal = Journal of Clinical Investigation | volume = 98 | issue = 8 | pages = 1888–1896|issn=0021-9738|pmid=8878441}}</ref> <ref name=":12">{{Cite journal | last = Hilgers | first = A. | last2 = Frank | first2 = J. | date = 1994 | title = [Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes] | url = https://pubmed.ncbi.nlm.nih.gov/7856214/ | journal = Wiener Medizinische Wochenschrift (1946) | volume = 144 | issue = 16 | pages = 399–406|issn=0043-5341|pmid=7856214}}</ref> | | |- |ssDNA (single-stranded DNA) |<ref name=":7">{{Cite journal | last = Vernon | first = Suzanne D | last2 = Reeves | first2 = William C | date = 2005-05-25 | title = Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome | url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/ | journal = Journal of Autoimmune Diseases | volume = 2 | pages = 5|doi=10.1186/1740-2557-2-5|issn=1740-2557|pmc=1177983|pmid=15916704}}</ref> | | |- |dsDNA (double-stranded DNA) | | | |- | | | | |- |'''Fatty Acid autoantibodies''' | | | |- |[[Oleic acid]] |<ref name=":8">{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivana | last3 = Leunis | first3 = Jean-Claude | date = Oct 2006 | title = Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins |url =https://pubmed.ncbi.nlm.nih.gov/17159817/ | journal = Neuro Endocrinology Letters | volume = 27 | issue = 5 | pages = 615–621|issn=0172-780X|pmid=17159817}}</ref> | | |- |[[Palmitic acid]] |<ref name=":8" /><ref name=":10">{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivana | last3 = Kubera | first3 = Marta | last4 = Leunis | first4 = Jean-Claude | last5 = Twisk | first5 = Frank N.M. | last6 = Geffard | first6 = Michel | date = Dec 2012 | title = IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression | url =https://pubmed.ncbi.nlm.nih.gov/22614823/ | journal = Metabolic Brain Disease | volume = 27 | issue = 4 | pages = 415–423|doi=10.1007/s11011-012-9316-8|issn=1573-7365|pmid=22614823}}</ref> | | |- |[[Myristic acid]] |<ref name=":8" /><ref name=":10" /> | | |- |'''Lipid peroxidation by-products''' | | | |- |Malondialdehyde (MDA) |<ref name=":8" /> | | |- |Azelaic acid |<ref name=":8" /> | | |- |'''N-oxide modified amino-acids''' | | | |- |NO-tyrosine |<ref name=":8" /> | | |- |NO-phenylalanine |<ref name=":8" /><ref name=":10" /> | | |- |NO-arginine |<ref name=":8" /> | | |- |NO-tryptophan |<ref name=":8" /> | | |- |NO-cysteinyl |<ref name=":8" /> | | |- | | | | |- |dUTPase |<ref>{{Cite journal | last = Halpin | first = Peter | last2 = Williams | first2 = Marshall Vance | last3 = Klimas | first3 = Nancy G. | last4 = Fletcher | first4 = Mary Ann | last5 = Barnes | first5 = Zachary | last6 = Ariza | first6 = Maria Eugenia | date = 2017 | title = Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology | url = https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24810 | journal = Journal of Medical Virology|language=en | volume = 89 | issue = 9 | pages = 1636–1645|doi=10.1002/jmv.24810|issn=1096-9071|pmc = 5513753|pmid=28303641}}</ref> | | |- |NO-Bovine serum albumin (nitro-BSA) |<ref>{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivana | last3 = Kubera | first3 = Marta | last4 = Leunis | first4 = Jean-Claude | date = Jun 2008 | title = An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS | url = https://pubmed.ncbi.nlm.nih.gov/18580855/ | journal = Neuro Endocrinology Letters | volume = 29 | issue = 3 | pages = 313–319|issn=0172-780X|pmid=18580855}}</ref> | | |- |Endothelial cells |30% (24 of 81)<ref name=":9">{{Cite journal | last = Ortega‐Hernandez | first = Oscar-Danilo | last2 = Cuccia | first2 = Mariaclara | last3 = Bozzini | first3 = Sara | last4 = Bassi | first4 = Nicola | last5 = Moscavitch | first5 = Samuel | last6 = Diaz‐Gallo | first6 = Lina-Marcela | last7 = Blank | first7 = Miri | last8 = Agmon‐Levin | first8 = Nancy | last9 = Shoenfeld | first9 = Yehuda | date = 2009 | title = Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome | url =https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2009.04802.x | journal = Annals of the New York Academy of Sciences|language=en | volume = 1173 | issue = 1 | pages = 589–599|doi=10.1111/j.1749-6632.2009.04802.x|issn=1749-6632}}</ref> | | |- |Neuronal cells |16% (13 of 81) <ref name=":9" /> | | |- |S-farnesyl-L-cysteine (AFC) |<ref name=":8" /><ref name=":10" /> | | |- |Oxidized LDL (oxLDL) |<ref>{{Cite journal | last = Maes | first = Michael | last2 = Kubera | first2 = Marta | last3 = Uytterhoeven | first3 = Marc | last4 = Vrydags | first4 = Nicolas | last5 = Bosmans | first5 = Eugene | date = Apr 2011 | title = Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) | url = https://pubmed.ncbi.nlm.nih.gov/21455120/ | journal = Medical Science Monitor: International Medical Journal of Experimental and Clinical Research | volume = 17 | issue = 4 | pages = SC11–15|doi=10.12659/msm.881699|issn=1643-3750|pmc=3539515|pmid=21455120}}</ref> | | |- |Thyroid peroxidase (TPO) |<ref name=":12" /> | | |- | | | | |- |68/48 kDa protein |13% (15 of 114); 0% controls<ref>{{Cite journal | last = Nishikai | first = M. | last2 = Tomomatsu | first2 = S. | last3 = Hankins | first3 = R.W. | last4 = Takagi | first4 = S. | last5 = Miyachi | first5 = K. | last6 = Kosaka | first6 = S. | last7 = Akiya | first7 = K. | date = Jul 2001 | title = Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders |url =https://pubmed.ncbi.nlm.nih.gov/11477286/ | journal = Rheumatology (Oxford, England) | volume = 40 | issue = 7 | pages = 806–810|doi=10.1093/rheumatology/40.7.806|issn=1462-0324|pmid=11477286}}</ref> | | |- |Antineutrophil cytoplasmic antibodies (ANCA) |47% (28 of 60)<ref>{{Cite journal | last = von Mikecz | first = A. | last2 = Konstantinov | first2 = K. | last3 = Buchwald | first3 = D.S. | 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/pubmed/9041942 | journal = Arthritis and Rheumatism | volume = 40 | issue = 2 | pages = 295–305|issn=0004-3591|pmid=9041942}}</ref> | | |- |HSP60 (Chlamydia pneumoniae peptide) |24% IgM 15 of 61)<ref>{{Cite journal | last = Elfaitouri | first = Amal | last2 = Herrmann | first2 = Björn | last3 = Bölin-Wiener | first3 = Agnes | last4 = Wang | first4 = Yilin | last5 = Gottfries | first5 = Carl-Gerhard | last6 = Zachrisson | first6 = Olof | last7 = Pipkorn | first7 = Rϋdiger | last8 = Rönnblom | first8 = Lars | last9 = Blomberg | first9 = Jonas | date = 2013 | title = Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis |url =https://www.ncbi.nlm.nih.gov/pubmed/24312270/ | journal = PloS One | volume = 8 | issue = 11| pages = e81155|doi=10.1371/journal.pone.0081155|issn=1932-6203|pmc=3842916|pmid=24312270}}</ref> | | |- |Microtubule-associated protein 2 (MAP2) |<ref name=":7" /> | | |}
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