Michael Cooperstock, MD, MPH
School of Medicine
University of Missouri Health System
Autoantibodies in chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a prolonged, seriously debilitating condition typically lasting many years. Even by the strictest definition, it is suffered by approximately 500,000 persons in the United States, mostly adolescent and adult women. Onset of CFS is often abrupt, associated with surgery, trauma, or an acute infection (e.g., respiratory, gastrointestinal, or infectious mononucleosis). The disorder is characterized by debilitating fatigue, usually worse for a day or two after moderate exercise. Many CFS patients also have features of autonomic nervous system instability, such as lightheadedness or fainting, or heart palpitations on standing. The cause of CFS is unknown, and there are no truly effective treatments.
Autoimmune theory: Several lines of evidence suggest CFS may be an autoimmune disorder. Its occurrence in previously healthy individuals, its relatively rapid onset, its persistence over many years, its relapsing-remitting course, and its marked female predominance are all clinical features of autoimmune disorders. Many cases are initiated by EB virus infection, an agent known to promote autoimmune processeses in lupus erythematosis and multiple sclerosis. Its apparent response to rituximab, which specifically eliminates antibody-producing B lymphocytes is also strongly suggestive. By analogy, autoantibodies to brain and dorsal root ganglia have been demonstrated in chronic post-Lyme disease syndrome, an entity essentially identical with chronic fatigue syndrome/fibromyalgia. Further, ultrasensitive proteomic analysis of spinal fluid from patients with both post-Lyme syndrome and CFS demonstrate c1 complement activation products, compatible with an ongoing antigen-antibody reaction in the central nervous system.
Study design: We propose a pilot study of 100 well-documented CFS patients and 100 controls, designed to determine if CFS is an autoimmune disorder. The study will test the patient sera for antibodies to a human neural cell line, antibodies to several specific human brain antigens by enzyme immunoassay, and to mouse brain and dorsal root ganglion tissue by both Western blot and immunohistochemistry. We will also determine if CFS patients with orthostatic symptoms have antibodies to vascular preparations and cholinergic and muscarinic autonomic receptors.