Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight

Rowley, Anne H.; Baker, Susan C.; Orenstein, Jan M.; Shulman, Stanford T.

doi:10.1038/nrmicro1853

Cited by 138 publications

(113 citation statements)

References 95 publications

(107 reference statements)

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“…To properly characterize the time lag between an air parcel leaving the presumed source region and having an influence on KD in the selected location, the air parcel crossing times were varied from the same day to 1 mo in advance of the date associated with the peak in KD cases. We allowed such a variety of lag times to give equal chance to any value in the range of the suspected lag times for the potential KD incubation time, both according to previous hypotheses and known times for airway diseases (13)(14)(15)(16). Average residence times were therefore computed for high and low KD dates and areas with residence times greater than the threshold for a high-residence time of 30 s in the preliminary high-low maps retained for further analyses (this threshold corresponds to 95% of the average simulated residence time; Data and Methods).…”

Section: Resultsmentioning

confidence: 99%

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

Rodó

Curcoll

Robinson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

183

155

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Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD.northeastern China source | agriculture | heart disease | FLEXPART | cereal croplands

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Section: Resultsmentioning

confidence: 99%

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

Rodó

Curcoll

Robinson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

183

155

View full text Add to dashboard Cite

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“…In Kawasaki disease, an unidentified infectious agent triggers hyper-activation and inflammation of the vascular and mucosal systems in genetically susceptible children [135]. Kawasaki disease can cause coronary aneurisms, and this is the most common cause of acquired heart disease in children in Japan and the US [136].…”

Section: Itpkc Polymorphisms Linked With Kawasaki Diseasementioning

confidence: 99%

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

Schell

2010

Cell. Mol. Life Sci.

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The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P(3)] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P(3). These enzymes terminate the signal to release Ca(2+) from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P(4)]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories.

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“…Because the clinical and epidemiologic features of KD support an infectious cause, one speculation is that the infectious agent travels from its portal of entry through the bloodstream and infects many organs and tissues; the immune response then targets these sites of infection. The theory of KD etiology that best fits the available data is that a ubiquitous infectious agent results in asymptomatic infection in most individuals but causes KD in a subset of genetically predisposed individuals (Rowley et al, 2008). Up to 25% of untreated children will develop persistent abnormalities in the coronary arteries; however, therapy with intravenous gammaglobulin and aspirin within the first ten days of fever onset reduces the prevalence of coronary artery abnormalities to approximately 5% (Newburger et al, 1986).…”

Section: Kawasaki Disease (Kd)mentioning

confidence: 89%