Chronic Fatigue
Syndrome
There is significant evidence indicating that chronic fatigue syndrome is a biological illness, which may be caused, in part, by an overactive immune system, often triggered by an infection.
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Autoimmune based chronic fatigue
Chronic fatigue: an immune dysfunction syndrome
Chronic fatigue: an immune dysfunction syndrome
Autoimmune based chronic fatigue

Autoimmune based chronic fatigue

Researchers believe that in some people, acute infections can elicit an abnormal autoimmune reaction, resulting in symptoms of chronic fatigue syndrome. Common infections including Epstein-Barr virus, herpes virus and the parvovirus B19, along with intracellular bacteria, are known to trigger the disease. 1

“In a subset of patients, ME/CFS [chronic fatigue syndrome] begins with infectious mononucleosis and evidence for a potential role of EBV in ME/CFS comes from many studies.” 1 In fact, Epstein–Barr virus and enterovirus are the two most common infectious triggers of CFS. 2

Furthermore, enteroviruses, such as coxsackie, cytomegalovirus (CMV), hepatitis C, Chlamydia pneumonia, and Coxiella burnetii have also been linked with chronic fatigue syndrome. 3 Upper respiratory infections, along with varicella-zoster virus, which causes chickenpox and shingles, have been implicated, as well. 4

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ME/CFS may be a variant of an autoimmune disease, writes Fluge et al. “It may involve antibodies, is often triggered by infections, and probably involves a genetic predisposition.” 5

Other studies have also suggested that infection-induced autoimmunity could be a possible disease mechanism. 5

Infections ignite an autoimmune attack

In response to an infection, the body’s immune system produces antibodies. Normally, the antibodies attack and kill any harmful outside substance (i.e. germ, bacteria). But in a subset of patients, these “autoantibodies” mistakenly attack healthy cells (or neurons) within the brain.

“Autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups, and infection by various pathogens … are known as triggers of [the] disease.” 1

This autoimmune attack causes inflammation in the brain and a range of symptoms, including extreme fatigue, brain fog, and other ME/CFS manifestations.

It is well-recognized that inflammation plays a role in Chronic Fatigue Syndrome. A study utilizing PET scans showed chronic fatigue syndrome patients had inflammation in specific regions of the brain (i.e., thalamus and amygdala), which the authors suggest could induce cognitive impairment and severe fatigue. 6

In a subset of patients, infections can throw the immune system into overdrive leading to symptoms of chronic fatigue syndrome. (8)

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Additionally, “Increased levels of the inflammatory biomarker, C-reactive protein, have been described in one of the largest CFS studies to date.” 7

“In the majority of ME/CFS cases, there is no conclusive evidence for chronic viral infection, but it is plausible that viruses could act via a “hit and run” mechanism.” 8

“This theory proposes that viruses trigger the disease, cause immune abnormalities and leave a dysfunctional immune system and/or autoimmunity.” 8

While the causative agents and disease mechanisms may vary, researchers agree there is strong evidence that chronic fatigue syndrome “is associated with a range of biological abnormalities, most notably in the neuroendocrine, autonomic, neurological, bioenergetic, redox and immunological domains.” 9

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  1. https://www.sciencedirect.com/science/article/pii/S1568997218300880 Franziska Sotzny, Julià Blanco, Enrica Capelli, Jesús Castro-Marrero, Sophie Steiner, Modra Murovska, Carmen Scheibenbogen. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease, Autoimmunity Reviews. Volume 17, Issue 6, 2018, Pages 601-609.
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921262/ Zhang L, Gough J, Christmas D, et al. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010;63(2):156–164.
  3. https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full Kerr, J. Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Front. Pediatr. 13 March 2019.
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702656/ Blomberg J, Rizwan M, Böhlin-Wiener A, et al. Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2019;10:1946.
  5. https://www.ncbi.nlm.nih.gov/pubmed/26132314 Fluge Ø, Risa K, Lunde S, et al. B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment. PLoS One. 2015;10(7):e0129898.
  6. http://jnm.snmjournals.org/content/early/2014/03/21/jnumed.113.131045.abstract Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune, and Yasuyoshi Watanabe. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. J Nucl Med. 2014 jnumed.113.131045 published ahead of print March 24, 2014.
  7. https://www.ncbi.nlm.nih.gov/pubmed/30567628 Russel A. et al. Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome. Psychoneuroendocrinology. 2019 Feb;100:276-285.
  8. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y Rasa, S. et al. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Journal of Translational Medicine. volume 16, Article number: 268 (2018).
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428797/ Morris G, Maes M, Berk M, Puri BK. Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?. Metab Brain Dis. 2019;34(2):385–415.
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CFS may be a variant of an autoimmune disease.

“ME/CFS may be a variant of an autoimmune disease.” 5

Infections may cause chronic fatigue immune syndrome
How can an infection cause chronic fatigue immune dysfunction syndrome symptoms?

Learn more about how infections can trigger neuropsychiatric symptoms

Cunningham Panel helps identify an autoimmune disorder in child initially diagnosed with schizophrenia

Cunningham Panel™ helps identify an autoimmune disorder in child initially diagnosed with schizophrenia

Researchers describe a complex case involving a 15-year-old girl, who abruptly developed multiple neurologic and psychiatric symptoms.

Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study

Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study

This nationwide, population-based, prospective cohort study examines the link between mood disorders, infections, and autoimmune disease.

Childhood infections can increase risk of mental illness in kids

Childhood infections can increase risk of mental illness in kids

Nationwide study finds both mild and severe infections can increase risk of mental disorders in children and adolescents.

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    The Cunningham Panel™ – Antibody testing that helps determine whether an autoimmune response may be triggering neurologic and/or psychiatric symptoms.
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B. Robert Mozayeni, MD

Medical and Clinical Advisor

B. Robert Mozayeni MD

Dr. B. Robert Mozayeni was trained in Internal Medicine and Rheumatology at Yale and at NIH. He has had pre- and post-doctoral Fellowships in Molecular Biophysics and Biochemistry at Yale, and also at NIH where he was a Howard Hughes Research Scholar at LMB/DCBD/NCI and later, Senior Staff Fellow at LMMB/NHLBI/NIH. Editorial board of Infectious Diseases – Surveillance, Prevention and Treatment. Past President of the International Lyme and Associated Diseases Society (ILADS).

He is an expert in Translational Medicine, the science and art of advancing medical science safely and efficiently. He is a Fellow of the non-profit Think Lead Innovate Foundation and is a co-founder of the Foundation for the Study of Inflammatory Diseases. He is a Founder of the Foundation for the Study of Inflammatory Diseases to crowd-source medical solutions for complex conditions using existing knowledge, diagnostic methods, and therapies to meet patient needs immediately. He is the Chief Medical Officer of Galaxy Diagnostics, LLC. He is a Board member of the Human-Kind Alliance. Dr. Mozayeni has held admitting privileges (since 1994) on the clinical staff of Suburban Hospital, a member of Johns Hopkins Medicine and an affiliate of the National Institutes of Health Clinical Center.

Safedin Sajo Beqaj, PhD, HCLD, CC (ABB)

Moleculera Labs, Clinical Laboratory Advisor
Medical Database, Inc., President and CEO

Sajo Baqaj, PhD

Dr. Sajo Beqaj is board certified in molecular pathology and genetics and licensed as a Bioanalyst and High Complexity Laboratory Director. He has been practicing as a laboratory director since 2005.

Dr. Beqaj served as a technical director and was part of the initial management team for several well-known laboratories in the clinical lab industry including PathGroup, Nashville, TN; DCL Medical Laboratories, Indianapolis, IN, and Pathology, Inc, Torrance, CA. He is currently serving as off-side CLIA laboratory director for BioCorp Clinical Laboratory, Whittier, CA and Health360 Labs, Garden Grove, CA.

Dr. Beqaj received his Ph.D. in Pathology from Wayne State University Medical School, Detroit, Michigan. He performed his post-doctoral fellowship at Abbott Laboratories from 2001-2003 and with Children’s Hospital and Northwestern University from 2003-2005.

Dr. Beqaj has taught in several academic institutions and has published numerous medical textbook chapters and journal articles. He has served as a principal investigator in clinical trials for several well-known pharmaceutical and diagnostic companies such as Roche HPV Athena, Merck HPV vaccine, BD vaginitis panel, Roche (Vantana) CINtec® Histology clinical trials, and has presented various scientific clinical abstracts and presentations.

He is a member of several medical and scientific associations including the Association of Molecular Pathology, American Association of Clinical Chemistry and the Pan Am Society for Clinical Virology. He has served on a number of clinical laboratory regulatory and scientific committees, and has assisted several laboratories and physicians as a Clinical Laboratory Consultant.