RNA-Containing Cytoplasmic Inclusion Bodies in Ciliated Bronchial Epithelium Months to Years after Acute Kawasaki Disease

Kawasaki Disease (KD) is the most common cause of acquired heart disease in children in developed nations. The KD etiologic agent is unknown but likely to be a ubiquitous microbe that usually causes asymptomatic childhood infection, resulting in KD only in genetically susceptible individuals. KD synthetic antibodies made from prevalent IgA gene sequences in KD arterial tissue detect intracytoplasmic inclusion bodies (ICI) resembling viral ICI in acute KD but not control infant ciliated bronchial epithelium. The prevalence of ICI in late-stage KD fatalities and in older individuals with non-KD illness should be low, unless persistent infection is common.Lung tissue from late-stage KD fatalities and non-infant controls was examined by light microscopy for the presence of ICI. Nucleic acid stains and transmission electron microscopy (TEM) were performed on tissues that were strongly positive for ICI. ICI were present in ciliated bronchial epithelium in 6/7 (86%) late-stage KD fatalities and 7/27 (26%) controls ages 9-84 years (p = 0.01). Nucleic acid stains revealed RNA but not DNA within the ICI. ICI were also identified in lung macrophages in some KD cases. TEM of bronchial epithelium and macrophages from KD cases revealed finely granular homogeneous ICI.These findings are consistent with a previously unidentified, ubiquitous RNA virus that forms ICI and can result in persistent infection in bronchial epithelium and macrophages as the etiologic agent of KD

Transmission electron microscopy (TEM) of ciliated bronchial epithelium from glutaraldehyde-fixed, previously frozen lung from KD patient 3.

<p>A) Lower power image demonstrating finely granular, variably electron-dense ICI (block arrows). N = nucleus, L = lysosomes, M = mitochondria, C = cilia. B) Higher power image of ICI (block arrows). Note rough endoplasmic reticulum (thin arrow). ICI are spherical and do not appear membrane-bound. A = 14,000X, B = 52,000X.</p

Patients with a history of Kawasaki Disease (KD) and the pathologic findings in their lungs.

<p>NA = not available, ND = not done, PE = pulmonary emboli, ARDS = acute respiratory distress syndrome, IHC = +indicates staining with antibody J but not antibody I,-indicates negative results with I and J</p

TEM of formalin-fixed, paraffin-embedded lung from KD patient 1.

<p>A, ciliated bronchial epithelium demonstrating electron-dense apical ICI (block arrows). B, alveolar macrophage, demonstrating perinuclear, finely granular spheroid bodies similar to those seen within the bronchial epithelium (block arrow). N = nucleus, C = cilia. A = 9,500X, B = 26,000X.</p

Controls and the pathologic findings in their lungs.

<p>NA = not available, COPD = chronic obstructive pulmonary disease, SLE = systemic lupus erythematosis, IHC = +indicates staining with antibody J but not antibody I,-indicates negative results with I and J</p

Peribronchial lymph node from KD patient 2.

<p>A, IHC using synthetic antibody J, showing antigen-positive macrophages containing spheroid bodies (arrows); B, transmission electron microscopy (TEM) of macrophage, showing two large, finely granular ICI (arrows). A = 40X, B = 20,000X.</p