Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.

Konstantinov, Konstantin N.; Mikecz, Anna von; Buchwald, Dedra; Jones, James F.; Gerace, Larry; Tan, Eng M.

doi:10.1172/jci118990

Cited by 123 publications

(63 citation statements)

References 34 publications

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“…A third study found no difference in the percentage of patients showing these abnormalities relative to controls (40) (v) Antinuclear antibodies. A number of papers have reported that CFS patients have a higher rate of autoantibody positivity than controls (3,27,48). However, a follow-up report using data from a number of CFS centers did not find similar differences between patients and controls (M. Sugiura, D. Daniels, D. Buchwald, A. Komaroff, M. Hossein, M. Peakman, S. Wessely, B. Natelson, I. Hay, P. Levine, and E. M. Tan, Abstr.…”

Section: Inconsistent Immune Markersmentioning

confidence: 99%

Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome

Natelson¹,

Haghighi

Ponzio

2002

Clin Vaccine Immunol

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Chronic fatigue syndrome is a medically unexplained ailment characterized by new onset of fatigue accompanied by rheumatological, infectious, and neuropsychiatric symptoms. Because the ailment often begins suddenly with a flu-like presentation, early pathophysiological ideas as to cause included viral infection and immune activation. When early reports identified putative immunological abnormalities in this illness, it was given the name of chronic fatigue and immune dysfunction syndrome, or CFIDS.The purpose of this review is to evaluate the immunological literature to determine if strong evidence to support this notion exists. We collected and reviewed 239 published papers, of which only 72 fulfilled a set of criteria for use in this review. For this review, we developed the following criteria: papers had to be published in the peer review literature; patients had to be from a group with substantial fatigue lasting at least 6 months (the vast majority fulfilled either the 1988 [21] or the 1994 [13] case definition of chronic fatigue syndrome [CFS]); papers had to compare CFS patients to healthy controls; and actual data had to be shown with evidence of testing for statistical significance. So, for example, when a paper reported no difference between patients and controls for some immunological variables but actual data were not included, we did not include it. Also, if a report compared patient data to normative values rather than to the study's own control group, we did not include it.The numbers of immunologically active cells and immunologically active substances such as cytokines reported in the literature have mushroomed in the past decade. To keep this review manageable, we are reporting scientific papers only on those variables for which either consistent or inconsistent abnormalities were reported by more than one group. We did not review papers reporting immunological variables to be within normal limits but have listed those studies in which more than one group found such results in a table. We have chosen not to list those variables reported abnormal in only one study because those results have not yet been replicated. When inconsistent results among laboratories were found for any immunological variable, we reviewed the methods described in those papers in an effort to identify reasons for such discrepancies.Note: when a group published more than one paper and it was apparent that the two studies used many if not all of the patients whose data are in the second paper, we chose to include only the more recent paper or the one with the largest number of subjects. To provide several examples, Tirelli published two papers, the first with 205 subjects and the second with 265 patients (66, 67). When data from one variable appeared in both papers, we included data from only the latter. Our own group has published three papers using different statistical methods and making different comparisons when reviewing lymphocyte populations. Thus, we used the one paper that controlled for multiple comparisons (74)...

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Section: Inconsistent Immune Markersmentioning

confidence: 99%

Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome

Natelson¹,

Haghighi

Ponzio

2002

Clin Vaccine Immunol

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“…The 27 proteins identified could be assigned to one of the following three groups. (i) Proteins already defined as TAAs such as grp78 [4], or proteins associated with autoaggressive immunity such as AH-NAK nucleoprotein [5], vimentin [6], and hsc70 [7]. (ii) Proteins of known function, which had not been associated with cancer (tropomyosin alpha, elongin A2).…”

Section: Resultsmentioning

confidence: 99%

Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology

Gires

Münz²,

Schaffrik³

et al. 2004

Cellular and Molecular Life Sciences (CMLS)

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We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.

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“…Combination of nuclear rim staining observed in indirect immunofluorescence microscopy and immunoblot analysis of highly purified proteins provided initial characterization of these autoantibodies. The occurrence of autoantibodies to a conserved intracellular protein, such as lamin B1, provided new laboratory evidence for an autoimmune component in chronic fatigue syndrome [Konstantinov et al, 1996;von Mikecz et al, 1997, reviewed in Bennet, 1998]. In addition, between 10 and 42% of patients with primary biliary cirrhosis have been reported to have antibodies against gp210, a glycoprotein of the nuclear pore complex (NPC) [Wesierska-Gadek et al, 1995;Bandin et al, 1996;Courvalin and Worman, 1997].…”

Section: Nuclear Envelopementioning

confidence: 99%

Antinuclear Autoantibodies: Fluorescent Highlights on Structure and Function in the Nucleus

Hemmerich

Mikecz

2000

Int Arch Allergy Immunol

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The eukaryotic nucleus is dynamically organized with respect to particular activities, such as RNA transcription, RNA processing or DNA replication. The spatial separation of metabolic activities is best reflected by the identification of functionally related proteins, in particular substructures of the nucleus. In a variety of human diseases, the integrity of such structures can be compromised, thus underlining the importance of a proper nuclear architecture for cell viability. Besides their clinical relevance, antinuclear autoantibodies (ANAs) have contributed to a large extent to the identification of subnuclear compartments, the isolation and cloning of their components (the autoantigens), as well a the characterization of their function. Although sophisticated techniques, such as confocal laser scanning microscopy (CLSM), fluorescence resonance energy transfer (FRET) and in vivo observation of cellular events have recently been established as valuable tools to study subnuclear architecture and function, cell biologists will continue to appreciate the specificity and power of ANAs for their research.

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Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.

Cited by 123 publications

References 34 publications

Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome

Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome

Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology

Antinuclear Autoantibodies: Fluorescent Highlights on Structure and Function in the Nucleus

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