Mechanisms of autoimmune disease induction

Behar, Samuel M.; Porcelli, Steven A.

doi:10.1002/art.1780380403

Cited by 80 publications

(7 citation statements)

References 120 publications

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“…The idea that superantigens may be an important factor in the pathogenesis of such diseases is supported by several studies [2,4,27]. MAS has been shown to exert a suppressive effect on lymphocyte function in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of the T cells is dependent only on the Vp chain and not on other variable elements of the TCR [3]. The recognition of superantigens by T cells may have several different consequences, including proliferation and expansion or the induction of anergy or even cell death [4]. However, the factors that determine which of these alternative reactions occur are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived fromMycoplasma arthritidis (MAS) and other mitogens

et al. 1997

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In this study we compared cytokine production and cell proliferation of immunocompetent cells derived from patients with ankylosing spondylitis (AS) to those from healthy blood donors using a whole blood assay. To this end, blood cell cultures were stimulated with the superantigens MAS (Mycoplasma arthritidis supernatant) and staphylococcal enterotoxin B (SEB) and the plant lectins phytohaemagglutinin (PHA) and concanavalin A (Con A). The number of white blood cells (WBC) and lymphocyte subsets were also determined. Cell proliferation and levels of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were measured after stimulation with the different mitogens. An ELISA test was used to analyse supernatant cytokine levels. Individuals with AS showed significantly lower IFN-gamma concentrations and markedly lower cell proliferation rates with all tested mitogens than healthy controls, while there was no significant difference in IL-6 synthesis. IL-1 beta levels were slightly impaired in the patient group, but only blood cell cultures stimulates with MAS showed a statistical significance. Furthermore, there was a significant elevation of leucocytes and lymphocytes in patients with AS resulting in higher numbers of CD4-positive cells, which implies a higher CD4:CD8 cell ratio. CD19- and CD8-positive cells were not significantly distinct compared to healthy controls. This deviation in cytokine levels and cell proliferation points to a suppression of T lymphocytes. A disturbed T-lymphocyte function may play a part in the pathogenesis of AS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived fromMycoplasma arthritidis (MAS) and other mitogens

et al. 1997

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“…The origins of autoimmunity, reflecting a failure of natural immune tolerance to self constituents of the body (autoantigens), have been long debated, for IDDM in particular [1,8] and for autoimmune disease in general [9,10]. Genotype is important, in that an age-dependent high risk is conferred by an appropriate constellation of susceptibility alleles, particularly those derived from the major histocompatibility complex (MHC) [1,8,11], specified as idd 1 [12].…”

mentioning

confidence: 99%

The GABA network and the pathogenesis of IDDM

Esposti

Mackay

1997

Diabetologia

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“…Retroviral infections in sheep (maedi/visna virus) and goats (caprine arthritis encephalitis) present a clinical picture similar to that of systemic human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis [40]. In mice strains susceptible to systemic lupus erythematosus (e.g.…”

Section: The Role Of Retrovirusesmentioning

confidence: 99%

“…Infectious agents can cause autoimmune diseases by different mechanisms as shown in Table 2 [14,40]. Roughly these mechanism fall into two categories: antigen specific in which pathogen products or elements have a central role e.g.…”

Section: Mechanisms Of Induction Of Autoimmune Diseases By Infectiousmentioning

confidence: 99%

The Role of Infections in the Pathogenesis of Autoimmune Diseases

Samarkos

Vaiopoulos

2005

CDTIA

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The autoimmune diseases result from inappropriate responses of the immune system to self antigens. The etiology of autoimmune diseases remains largely unknown but candidate etiologic factors include genetic abnormalities and infections. Although there are considerable data supporting the role of infections in a variety of autoimmune diseases, this role has been unequivocally established in only a few autoimmune diseases. The difficulty in establishing the infectious etiology of autoimmune diseases stems from several factors such as the heterogeneity of clinical manifestations in individual autoimmune diseases and the time interval between infection and autoimmune disease. The data on this association derive from clinical observations, epidemiological studies and research using laboratory techniques, protein sequence database screening and animal models. Infectious agents can cause autoimmune diseases by different mechanisms, which fall into two categories: antigen specific in which pathogen products or elements have a central role e.g. superantigens or epitope (molecular) mimicry, and antigen non-specific in which the pathogen provides the appropriate inflammatory setting for "bystander activation". The most important mechanisms are molecular mimicry and superantigens. As far as molecular mimicry is concerned the recent data on the degeneracy of T cell recognition shifted the focus from searching for linear sequence homology to looking for similarity of antigenic surfaces. Special mention has to be made to retroviruses as they have some unique means of inducing autoimmunity.

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Mechanisms of autoimmune disease induction

Cited by 80 publications

References 120 publications

Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived fromMycoplasma arthritidis (MAS) and other mitogens

Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived fromMycoplasma arthritidis (MAS) and other mitogens

The GABA network and the pathogenesis of IDDM

The Role of Infections in the Pathogenesis of Autoimmune Diseases

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