Tag: autoantibodies

Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression

Abstract:

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients.

Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms ofchronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear.

Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.

 

Source: Wheatland R. Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65(2):287-95. http://www.ncbi.nlm.nih.gov/pubmed/15885924

 

Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders

Abstract:

OBJECTIVE: To identify antinuclear antibodies (ANA) specific for chronic fatigue syndrome (CFS), and in related conditions such as fibromyalgia (FM) or psychiatric disorders.

METHODS: One hundred and fourteen CFS patients and 125 primary and secondary FM patients were selected based on criteria advocated by the Centers for Disease Control and Prevention and by the American College of Rheumatology, respectively. As controls, healthy subjects and patients with either various psychiatric disorders or diffuse connective tissue diseases were included. Autoantibodies were examined by immunoblot utilizing HeLa cell extracts as the antigen.

RESULTS: Autoantibodies to a 68/48 kDa protein were present in 13.2 and 15.6% of patients with CFS and primary FM, respectively. In addition, autoantibodies to a 45 kDa protein were found in 37.1 and 21.6% of the patients with secondary FM and psychiatric disorders, respectively. Meanwhile, these two autoantibodies were not found at all in connective tissue disease patients without FM, nor in healthy subjects (P<0.05). As a group, the anti-68/48 kDa-positive CFS patients presented more frequently with hypersomnia (P<0.005), short-term amnesia (P<0.07) or difficulty in concentration (P<0.05) than those CFS patients without the antibodies.

CONCLUSIONS: The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and cognitive complaints.

 

Source: Nishikai M, Tomomatsu S, Hankins RW, Takagi S, Miyachi K, Kosaka S, Akiya K. Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders. Rheumatology (Oxford). 2001 Jul;40(7):806-10. http://rheumatology.oxfordjournals.org/content/40/7/806.long (Full article)

 

Single aetiological agent may not be feasible in CFS patients

Comment on: Cortisol deficiency may account for elevated apoptotic cell population in patients with chronic fatigue syndrome. [J Intern Med. 1999]

 

Dear Sir, I would like to thank Dr Baschetti for his very interesting letter. I hope clinicians and CFS patients will be able to benefit from its contents. We agree that chronic fatigue syndrome (CFS) is an illness with uncertain aetiology. Although it is true that no single infectious agent has been identified as a primary cause of CFS, a variety of pathogens, including HTLV-II, EBV, cytomegalovirus, herpes simplex viruses 1 and 2, and human herpes viruses 6, 7 and 8, have been identified in CFS patients [1–7]. In addition to the pathogens previously mentioned, a recent study by our laboratory has identified Mycoplasma fermentans in a statistically significant number of CFS patients over non-CFS control subjects [8]. Further investigation is necessary to determine whether these pathogens are occurring secondarily to some immunological disturbances, as some investigators believe, or whether they are involved as a primary cause of symptoms characteristic of CFS. As mentioned by Dr Baschetti, various measures of immune function have been reported to be altered in CFS subjects, thereby suggesting an association rather than demonstrating a causative link. Abnormalities that have been reported include increased circulating immune complexes, reduced CD4 and CD8 T-lymphocyte subsets, diminished natural killer cell activity, reduction in IgG subclasses, reduced mitogenic response of lymphocytes, altered cytokine production, elevated titres of antibodies to a number of viruses and abnormal production of IFN [9–15]. However, similar immune functional abnormalities have been reported in patients exposed to toxic chemicals without evidence of viral infection or reactivation [16, 17]. Moreover, the symptomatologies described in these patients overlap with CFS patients, thus making the differentiation between the two groups extremely difficult [18–21]. In these articles, the substantial overlap between chemical sensitivity, fibromyalgia and CFA was discussed. It was concluded that the latter two conditions may involve chemical sensitivity and may even be the same disorder. In fact, in a separate study strictly with CFS patients without evidence of viral reactivation but exposed to methyl tertiary-butyl ether (MTBE) and benzene, we showed that programmed cell death and cell cycle were abnormal in both groups [22]. Similarly, in our original article published in this journal, we reported elevated apoptosis and abnormal cell cycle in CFS patients without a history of exposure to toxic chemicals. The interferon-induced protein kinase RNA (PKR) was found to be elevated in these patients as well and was therefore proposed as a possible mechanism of induction of apoptosis and cell cycle abnormalities [23].

 

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.1999.00479.x/full

 

Source: Vojdani A. Single aetiological agent may not be feasible in CFS patients. J Intern Med. 1999 Apr;245(4):410-2. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.1999.00479.x/full

 

Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss

Abstract:

Immunoserological assays of patients with sudden deafness and progressive hearing losses have revealed the presence of different antibodies, leading to the assumption that immunological processes may be involved. Recent investigations have demonstrated that these patients have phospholipid antibodies that can cause venous or arterial vasculopathies.

In the present study we analyzed the incidence of these antibodies in patients with inner ear disorders. Sera of 55 patients with sudden deafness and 80 patients with progressive hearing loss were tested.

Phospholipid antibodies were demonstrable in 49% of the patients with sudden hearing loss and 50% of the patients with progressive hearing loss. Serotonin and ganglioside antibodies were found in 53% of the patients with sudden hearing loss and 63% of the patients with progressive hearing loss.

Since these three antibodies are also frequently found in patients with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS), 28 of the patients studied displayed symptoms typical for these disorders, including fatigue, myalgia, arthralgia, depressions, sicca symptoms and diarrhea.

We now recommend questioning patients suffering from inner ear disorders for symptoms typical for FMS or CFS, since these diseases are often closely related to inner ear disorders. If symptoms are present, antibodies should be tested against phospholipids, serotonin and gangliosides. If present, the antibodies are diagnostic for each syndrome. Additionally these immunologic and serologic findings show that these antibodies may play a role in the etiology of hearing loss disorders.

 

Source: Heller U, Becker EW, Zenner HP, Berg PA. Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss. HNO. 1998 Jun;46(6):583-6. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/9677490

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain

Abstract:

Epidemiologic studies continue to provide evidence that fibromyalgia is part of a spectrum of chronic widespread pain. The prevalence of chronic widespread pain is several times higher than fibromyalgia as defined by the 1990 American College of Rheumatology guidelines. There is now compelling evidence of a familial clustering of fibromyalgia cases in female sufferers; whether this clustering results from nature or nature remains to be elucidated. A wide spectrum of fibromyalgia-associated symptomatology and syndromes continues to be described.

During the past year the association with interstitial cystitis has been explored, and neurally mediated hypotension has been documented in both fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone-insulin-like growth factor-1 axis have been also documented in both fibromyalgia and chronic fatigue syndrome. The commonly reported but anecdotal association of fibromyalgia with whiplash-type neck trauma was validated in a report from Israel. However, unlike North America, 100% of Israeli patients with posttraumatic fibromyalgia returned to work.

Basic research in fibromyalgia continues to pinpoint abnormal sensory processing as being integral to understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D-aspartate receptors (which are often upregulated in central pain states) were shown to benefit fibromyalgia pain in an experimental setting. The combination of fluoxetine and amitriptyline was reported to be more beneficial than either drug alone in patients with fibromyalgia.

A high prevalence of autoantibodies to cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome, and an increased prevalence of antipolymer antibodies was found in symptomatic silicone breast implant recipients who often have fibromyalgia.

 

Source: Bennett R. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. Curr Opin Rheumatol. 1998 Mar;10(2):95-103. http://www.ncbi.nlm.nih.gov/pubmed/9567202

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214