RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Rowley
Anne H
AH
Department of Pediatrics, Northwestern University Feinberg School of Medicine, The Center for Kawasaki Disease, The Children's Memorial Hospital, Chicago, Illinois, USA. a-rowley@northwestern.edu
Baker
Susan C
SC
Shulman
Stanford T
ST
Garcia
Francesca L
FL
Fox
Linda M
LM
Kos
Ian M
IM
Crawford
Susan E
SE
Russo
Pierre A
PA
Hammadeh
Rashid
R
Takahashi
Kei
K
Orenstein
Jan M
JM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D006801:Humans; D002479:Inclusion Bodies / Q000821:virology*; D007231:Infant, Newborn; D016676:Macrophages, Alveolar / Q000473:pathology / Q000821:virology*; D008853:Microscopy; D008875:Middle Aged; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology / Q000473:pathology / Q000821:virology*; D012328:RNA Viruses; D012367:RNA, Viral / Q000032:analysis; D020545:Respiratory Mucosa / Q000473:pathology / Q000821:virology*
D012367:RNA, Viral