Tag: autoimmunity

The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity

Abstract:

The authors compared in a group of 118 patients with autoimmune thyroiditis and a positive antibody titre against ovaries the grade of fatigue with the presence of organ specific and non-specific autoantibodies in the peripheral blood stream, antibodies against EBV and CMV, immunoglobulin concentrations, biochemical parameters of the lipid metabolism, glucose tolerance, ion balance and melatonin and serotonin levels. Patients with autoimmune thyroiditis were differentiated according to the degree of fatigue into three groups: 38 with fatigue typical for CFS, 30 with occasional fatigue and 50 without the feeling of fatigue.

Fatigue of the CFS type was characterized by a significantly higher incidence of autoantibodies against the adrenals and a higher cholesterol level. Increased fatigue of the patients was associated with a lower melatonin level, a higher serotonin level and a lower M/S ratio as compared with patients without fatigue. In other indicators no differences were found. Fatigue in CFS could be associated, similarly as in autoimmune endocrinopathies, with impaired immunoendocrine regulation. In autoimmune thyroiditis, regardless of the concomitant presence of fatigue, in addition to antibodies against thyroid peroxidase most frequently antibodies against the ovaries were detected.

 

Source: Sterzl I, Fucíková T, Hrdá P, Matucha P, Zamrazil V. The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity. Vnitr Lek. 1998 Aug;44(8):456-60. [Article in Czech] http://www.ncbi.nlm.nih.gov/pubmed/10358448

 

Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome

Abstract:

 

Chronic fatigue syndrome (CFS) patients suffer from disabling physical and mental fatigue. Circulating autoimmune antibodies may produce symptoms of muscular fatigue by reacting with acetylcholine receptors or calcium binding channels. They can also produce mental status changes by reacting with central nervous system (CNS) antigens. We thoroughly investigated the presence of circulating antimuscle and anti-CNS antibodies in 10 CFS patients and 10 controls. We were unable to detect any pathogenic antibodies.

 

Source: Plioplys AV. Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome. Neurology. 1997 Jun;48(6):1717-9. http://www.ncbi.nlm.nih.gov/pubmed/9191795

 

High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies.

METHODS: Initial immunofluorescence histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate.

RESULTS: Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty-eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%).

CONCLUSION: The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.

Comment in: Incidence of antinuclear antibodies in Japanese patients with chronic fatigue syndrome. [Arthritis Rheum. 1997]

 

Source: von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM. High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome. Arthritis Rheum. 1997 Feb;40(2):295-305. http://www.ncbi.nlm.nih.gov/pubmed/9041942

 

Gender differences in host defense mechanisms

Abstract:

Extensive studies in both humans and animals have shown that females express enhanced levels of immunoreactivity compared to males. Whereas this provides females with increased resistance to many types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on gender-related differences in non-specific host defense mechanisms with a particular emphasis on monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1). Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally, these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome (CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in immune function to find a key for this poorly understood syndrome.

 

Source: Cannon JG, St Pierre BA. Gender differences in host defense mechanisms. J Psychiatr Res. 1997 Jan-Feb;31(1):99-113. http://www.ncbi.nlm.nih.gov/pubmed/9201652

 

Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome

Abstract:

We have identified and partially characterized the autoantibodies in sera of 60 patients with chronic fatigue syndrome. Approximately 52% of the sera were found to react with nuclear envelope antigens.

The combination of nuclear rim staining observed in immunofluorescence microscopy and immunoblot analysis of highly purified nuclear envelope proteins provided initial characterization of these autoantibodies. Further characterization showed that some sera immunoprecipitated the in vitro transcription and translation product of a human cDNA clone encoding the nuclear envelope protein lamin B1. The autoantibodies were of the IgG isotype.

The occurrence of autoantibodies to a conserved intracellular protein like lamin B1 provides new laboratory evidence for an autoimmune component in chronic fatigue syndrome.

 

Source: Konstantinov K, von Mikecz A, Buchwald D, Jones J, Gerace L, Tan EM. Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome. J Clin Invest. 1996 Oct 15;98(8):1888-96. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507629/ (Full article)

 

‘Seronegative’ Sjögren’s syndrome manifested as a subset of chronic fatigue syndrome

Abstract:

We determined the extent to which chronic fatigue syndrome (CFS) patients with sicca symptoms fulfil the diagnostic criteria for Sjögren’s syndrome (SS). Three sets of diagnostic criteria for SS, formulated by the Japanese, Europeans and Fox, were used. One-third of the CFS patients with sicca symptoms fulfilled the diagnostic criteria for SS. However, they were ‘seronegative’, differing from the ordinary primary SS.

 

Source: Nishikai M1, Akiya K, Tojo T, Onoda N, Tani M, Shimizu K. ‘Seronegative’ Sjögren’s syndrome manifested as a subset of chronic fatigue syndrome. Br J Rheumatol. 1996 May;35(5):471-4. http://rheumatology.oxfordjournals.org/content/35/5/471.long (Full article)

 

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

Abstract:

The fibromyalgia syndrome (FMS) is one of the most frequent rheumatic disorders showing a wide spectrum of different symptoms. An association with the chronic fatigue syndrome (CFS) has been discussed. Recently, a defined autoantibody pattern consisting of antibodies to serotonin (5-hydroxytryptamine, 5-HT), gangliosides and phospholipids was found in about 70% of the patients with FMS. We were therefore interested in seeing whether patients with CFS express similar humoral immunoreactivity.

Sera from 42 CFS patients were analysed by ELISA for these antibodies, and the results were compared with those previously observed in 100 FMS patients. 73% of the FMS and 62% of the CFS patients had antibodies to serotonin, and 71% or 43% to gangliosides, respectively. Antibodies to phospholipids could be detected in 54% of the FMS and 38% of the CFS patients. 49% of FMS and 17% of the CFS patients had all three antibodies in parallel, 70% and 55%, respectively had at least two of these antibody types. 21% of FMS and 29% of CFS patients were completely negative for these antibodies. Antibodies to 5-HT were closely related with FMS/CFS while antibodies to gangliosides and phospholipids could also be detected in other disorders.

The observation that family members of CFS and FMS patients also had these antibodies represents an argument in favour of a genetic predisposition. These data support the concept that FMS and CFS may belong to the same clinical entity and may manifest themselves as ‘psycho-neuro-endocrinological autoimmune diseases’.

 

Source: Klein R, Berg PA. 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. Eur J Med Res. 1995 Oct 16;1(1):21-6. http://www.ncbi.nlm.nih.gov/pubmed/9392689

 

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

 

 

Review of laboratory findings for patients with chronic fatigue syndrome

Abstract:

Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen.

 

Source: Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S12-8. http://www.ncbi.nlm.nih.gov/pubmed/1902321