Abstract:
:Recently, a single nucleotide polymorphism (SNP) of the inositol 1,4,5-triphosphate kinase C (ITPKC), rs28493229, was found to passively confer susceptibility for Kawasaki syndrome (KS) and subsequent coronary arterial lesions. This association is believed to be the result of defective phosphorylation of inositol 1,4,5-triphosphate (IP3), which releases calcium from intracellular stores, resulting from reduced genetic expression of ITPKC in carriers of the SNP. Reduced ITPKC activity would increase IP3 levels, and thus, increase calcium release. We hypothesized that an environmental agent which influences IP3-mediated calcium release is potentiated by the ITPKC SNP. This led us to an attractive candidate, thimerosal, an organomercurial medical preservative still used in several pediatric vaccines. Thimerosal is well-known to sensitize IP3 receptors via its induction of oxidative stress, resulting in enhanced release of intracellular calcium with distinctive consequences for various cell types. Dysregulated calcium signaling in T cells and other immune cells can result in autoimmunity, while hyperpolarization of vascular smooth muscle cells secondary to the stimulation of calcium-activated potassium channels can result in increased vascular permeability and arterial relaxation. We propose that ITPKC susceptibility in KS is related to its synergy with environmental triggers, such as thimerosal, which alter calcium homeostasis and promote oxidative stress. Therefore, carriers of the ITPKC SNP are more susceptible to thimerosal-induced autoimmunity and coronary arterial lesions observed in KS. This would explain why only a susceptible subset of children develops KS although pediatric thimerosal exposure is nearly universal due to vaccination. As was experienced with the infantile acrodynia epidemic, only 1 in 500 children developed the disease although pediatric mercury exposure was nearly ubiquitous due to the use calomel teething powders. This hypothesis also mirrors the current leading theory for KS in which a widespread infection only induces the disease in susceptible children. We conclude that KS may be the acute febrile form of acrodynia.
journal_name
Autoimmun Revjournal_title
Autoimmunity reviewsauthors
Yeter D,Deth Rdoi
10.1016/j.autrev.2012.03.006subject
Has Abstractpub_date
2012-10-01 00:00:00pages
903-8issue
12eissn
1568-9972issn
1873-0183pii
S1568-9972(12)00075-4journal_volume
11pub_type
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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更新日期:2016-08-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2004.04.002
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章
doi:10.1016/j.autrev.2009.02.002
更新日期:2009-06-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2004.07.006
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2007.03.008
更新日期:2007-08-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章
doi:10.1016/j.autrev.2020.102660
更新日期:2020-11-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2008.07.027
更新日期:2008-10-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2006.12.001
更新日期:2007-09-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/S1568-9972(03)00091-0
更新日期:2004-02-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2018.01.004
更新日期:2018-03-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2013.03.001
更新日期:2013-07-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2009.10.004
更新日期:2010-01-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2014.10.012
更新日期:2015-02-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2004.04.001
更新日期:2004-06-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,收录出版,评审
doi:10.1016/j.autrev.2019.05.005
更新日期:2019-07-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2018.06.006
更新日期:2018-11-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2009.11.018
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2017.10.003
更新日期:2017-12-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,meta分析
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更新日期:2019-11-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2008.11.006
更新日期:2009-02-01 00:00:00
abstract::To date, no immunomodulatory drug has proved efficacious in primary Sjögren's syndrome (pSS). In pSS, difficulties in drug efficacy assessment is related to the large spectrum of clinical involvements (glandular/extraglandular involvement), to the lack of correlation between symptoms of dryness and glandular function ...
journal_title:Autoimmunity reviews
pub_type: 杂志文章
doi:10.1016/j.autrev.2018.12.008
更新日期:2019-06-01 00:00:00
abstract::There is a thriving interest in the field of hereditary autoinflammatory disorders (HAID), a gamut of heterogeneous conditions deriving from an aberrant orchestration of innate immunity, unified by the common feature of seemingly unprovoked inflammation, which might be systemic or occur in localized niches of the orga...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2014.08.001
更新日期:2014-09-01 00:00:00
abstract::Self-reactive antibodies represent a significant force in autoimmune disease induction. In antibody-dependent autoimmune syndromes such as immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), myasthenia gravis and rheumatoid arthritis (RA), autoantibodies exert their inflammatory effect through FcγRs, a ...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2016.02.006
更新日期:2016-06-01 00:00:00
abstract::The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of diseases causing inflammation in small blood vessels and linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). These antigens are present both in the cytoplasmic granu...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2016.07.031
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:Since characterization of the extent to which particular combinations of autoimmune diseases (ADs) occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms, polyautoimmunity (i.e., ADs co-occurring within patients) in systemic lupus erythematosus (SL...
journal_title:Autoimmunity reviews
pub_type: 杂志文章
doi:10.1016/j.autrev.2009.10.001
更新日期:2010-02-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2018.06.007
更新日期:2018-11-01 00:00:00
abstract::Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) remains the hallmark of diagnosing autoimmune diseases despite the introduction of multiplex techniques. Non-organ specific AAB are screened in routine diagnostics by IIF on HEp-2 cells. However, IIF results vary due to objective (e.g., cell fixatio...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2009.02.033
更新日期:2009-09-01 00:00:00
abstract::Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2016.02.005
更新日期:2016-07-01 00:00:00