Toxicology of Autoimmune Diseases

Pollard, K. Michael; Hultman, Per; Kono, Dwight H.

doi:10.1021/tx9003787

Cited by 98 publications

(74 citation statements)

References 168 publications

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“…This systemic autoimmune disease is characterized by lymphoproliferation, hypergammaglobulinaemia, autoantibodies and glomerulonephritis. 12,13 Development of mHgIA is dependent upon T cells, particularly CD4 + T cells 14 and results in the presence of interleukin-4 (IL-4) producing type 2 CD4 + T helper cells. 15 However, mHgIA is initiated in the absence of IL-4 16,17 but interferon-c (IFN-c) is required.…”

Section: Discussionmentioning

confidence: 99%

Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

2012

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Summary Deficiency in Daf1, a complement regulatory protein, has been shown to exacerbate development of various autoimmune diseases and recent studies have suggested that this may be explained by Daf1 acting to limit T‐cell hyper‐responsiveness. It has been suggested that the absence of Daf1 aggravates autoimmune disease in a complement‐dependent manner, but others have shown that activation of T cells in the absence of Daf1 can be complement independent. However, the relationship between Daf1, complement components, lymphocyte activation, cytokine expression and antibody production remains to be determined in mice that are not Daf1 deficient. We have recently demonstrated, in murine mercury‐induced autoimmunity (mHgIA), that an accumulation of CD44high Daflow CD4+ T cells is associated with the development of autoimmunity. In this study we observed that complement depletion does not affect the accumulation of activated CD4+ T cells, elevation of splenic interleukin‐4 expression and autoantibody production in mHgIA. In addition, neither the accumulation of CD44high Daflow CD4+ T cells nor the down‐regulation of Daf1 expression on CD4+ T cells was influenced by a lack of complement. In conclusion, these studies show that initiating events in xenobiotic‐induced autoimmunity, including lymphocyte activation, cytokine expression and autoantibody production, are not dependent on complement.

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Section: Discussionmentioning

confidence: 99%

Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

2012

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“…Certain mouse strains possessing specific H2 (the murine counterpart for HLA) haplotypes develop a nonSSc autoimmune disease and high titer AFA following administration of mercuric chloride or silver nitrate (31)(32)(33)(34). Of note, one study of urinary mercury levels in SSc patients noted higher levels in those with AFA.…”

Section: Discussionmentioning

confidence: 99%

Anti-Fibrillarin Antibody in African American Patients with Systemic Sclerosis: Immunogenetics, Clinical Features, and Survival Analysis

2011

J Rheumatol

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“…Many peptide fragments of microbial agents are homologous with host proteins, and the induction of an immune response to these antigens can result in cross-reactivity with self-antigens and the induction of autoimmunity. A number of chemicals and therapeutic agents have been identified as potential triggers for autoimmunity and have been suggested to both induce onset and modulate disease severity [7,108]. While it is believed that a genetic predisposition to self-reactivity exists in all individuals with autoimmune diseases, differing susceptibility factors may govern the timing or specific disease an individual develops.…”

Section: Autoimmunitymentioning

confidence: 99%

Immunotoxicology and Its Application in Risk Assessment

Rooney

Luebke

Selgrade

et al. 2012

Experientia Supplementum

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Immunotoxicology is the study of undesired modulation of the immune system by extrinsic factors. Toxicological assessments have demonstrated that the immune system is a target following exposure to a diverse group of xenobiotics including ultraviolet radiation, chemical pollutants, therapeutics, and recreational drugs. There is a well-established cause and effect relationship between suppression of the immune response and reduced resistance to infections and certain types of neoplasia. In humans, mild-to-moderate suppression of the immune response is linked to reduced resistance to common community-acquired infections, whereas opportunistic infections, which are very rare in the general population, are common in individuals with severe suppression. Xenobiotic exposure may also result in unintended stimulation of immune function. Although a cause and effect relationship between unintended stimulation of the immune response and adverse consequences has yet to be established, evidence does suggest that hypersensitivity, autoimmunity, and pathological inflammation may be exacerbated in susceptible populations exposed to certain xenobiotics. Xenobiotics can act as allergens and elicit hypersensitivity responses, or they can modulate hypersensitivity responses to other allergens such as pollen or dust mite by acting as adjuvants, enhancing the development or expression of hypersensitivity. Allergic contact dermatitis, allergic rhinitis, and asthma are the most commonly encountered types of hypersensitivity reactions resulting from chemical exposure. The immunologic effectors and mechanisms involved in autoimmune reactions are the same as those associated with responses to foreign antigens; however, the reactions are directed against the host's own cells. Thus, chemicals that induce immune suppression, nonspecific immunostimulation, or hypersensitivity may also impact autoimmunity. Risk assessment for immunotoxicity should be performed using the same approaches and principles for other noncancer effects. However, since xenobiotics may have effects on more than one aspect of immune function, immunotoxicity data should be evaluated separately for evidence of suppression, stimulation, hypersensitivity, and autoimmunity.

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Toxicology of Autoimmune Diseases

Cited by 98 publications

References 168 publications

Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

Anti-Fibrillarin Antibody in African American Patients with Systemic Sclerosis: Immunogenetics, Clinical Features, and Survival Analysis

Immunotoxicology and Its Application in Risk Assessment

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