The IgA Response in Acute KD Targets Inclusion Bodies in KD Ciliated Bronchial Epithelium ROWLEY, ANNE H. (NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE AND CHILDREN’S MEMORIAL HOSPITAL, CHICAGO, IL.) 【AIM】We have reported an antigen-driven IgA immune response in the arterial wall in acute KD. We made KD synthetic antibodies using IgA sequences prevalent in acute KD arterial tissue and used these antibodies in immunohistochemistry experiments on acute KD and infant control tissues, to determine if a target antigen was present in acute KD tissues. The antibodies identified antigen in acute KD but not infant control ciliated bronchial epithelium, and in a subset of macrophages in acute inflamed KD tissues. Light and electron microscopy revealed that the antigen in acute KD ciliated bronchial epithelium localized to intracytoplasmic inclusion bodies (ICI) consistent with aggregates of viral proteins and nucleic acids. We hypothesized that ICI would only be present in KD tissues during the first two months after onset, when inflammation is present. However, if the KD agent were latent or persistent, ICI could be present late after KD, and could be present in control individuals, who could have been infected with the agent asymptomatically. 【MATERIAL】We examined lung tissues from 7 KD patients who died > 10 weeks after the onset of acute KD and 27 non-infant controls by immunohistochemistry using KD synthetic antibodies, to determine whether ICI could be detected. Nucleic acid stains and transmission electron microscopy (TEM) were performed on tissues that were strongly positive for ICI. 【RESULTS】ICI were present in bronchial epithelium in 3/7 late-stage KD fatalities, in 24-year old patient 1 who died 21 years after acute KD, 8 year-old patient 2 who died 15 months after acute KD, and 19-month-old patient 3 who died 9 months after KD. In patients 1 and 2, nucleic acid stains revealed RNA but not DNA within the ICI, and TEM revealed finely granular ICI. Antigen was detected in lung macrophages in all 3 KD cases with ICI in ciliated bronchial epithelium. In KD patient 2, antigen-positive macrophages were present in the myocardium in an area of myocardial dropout. ICI were detected in lung in 7 of 27 controls ages 9-84 years. 【CONCLUSIONS】The presence of RNA and not DNA within the ICI suggests that the KD agent is an RNA virus. The detection of ICI in ciliated bronchial epithelium and KD antigen in macrophages in lung and myocardium months to years after acute KD suggests that the agent can be persistent in at least a subset of KD patients. The finding that about 25% of older childhood and adult control lungs show ICI is consistent with a ubiquitous infectious agent that can persist both in KD patients and in those who experience asymptomatic infection. Fresh lung and coronary artery tissue from KD fatalities are needed for molecular studies and for direct placement into glutaraldehyde for optimal ultrastructural experiments, to determine whether the ICI represent aggregates of viral nucleocapsids or other structures, and to determine the structure of any viral particles that may be present in cells containing ICI.