The rough endoplasmic reticulum and the Golgi complex are mostly apical and are adjacent to the nucleus

The rough endoplasmic reticulum and the Golgi complex are mostly apical and are adjacent to the nucleus. are consistent with aggregates of viral proteins and associated nucleic acid and may derive from the FRAX1036 etiologic agent of KD Kawasaki disease FRAX1036 (KD) is an acute systemic inflammatory illness of early childhood that particularly affects medium-sized arteries, such as the coronary arteries, and that can result in myocardial infarction, coronary artery aneurysms that rupture, and sudden death [1]. In developed nations, KD has replaced acute rheumatic fever as the most common cause of acquired heart disease in children [2]. Although the etiology is unknown, clinical and epidemiologic data support infection with a ubiquitous microbial agent. This theory predicts that most individuals are asymptomatically infected with the agent during child years and that only a very small subset of genetically predisposed individuals develop clinical features of KD. With this model, the rarity of KD in babies 3 months aged is explained by protective, passive maternal antibodies. The rarity of KD in adults is definitely consistent with common immunity. Attempts to identify the etiologic agent of KD by traditional methods have not been successful Our laboratory offers taken an immunologic approach to the investigation of the etiology of KD. We have discovered that IgA plasma cells infiltrate coronary arteries [3] and additional inflamed cells during acute KD [4] and that, compared with control subjects, peribronchial IgA plasma cells are significantly increased in the top respiratory tracts of individuals with acute KD, which is similar to findings in children with fatal viral respiratory infections [4]. We have also reported that macrophages and CD8 T lymphocytes are prominent in the inflammatory infiltrate [5]. These immunologic findings suggest the presence of an intracellular pathogen having a respiratory portal of access IgA genes in arteries from individuals with acute fatal KD are oligoclonal, that is, are antigen driven [6]. We previously made oligoclonal KD antibodies in vitro and performed immunohistochemical experiments on formalin-fixed, paraffin-embedded cells from individuals with acute KD and from control subjects, ISGF3G and we reported that synthetic KD antibody A recognized antigen in acute KD, but not in control, bronchial epithelium as well as with a subset of macrophages in inflamed acute KD cells, such as the coronary arteries [7]. Antigen was localized to unique perinuclear, primarily apical intracytoplasmic spheroidal body in acute KD ciliated bronchial epithelium by use of synthetic KD antibody A. To further characterize this antigen in acute KD bronchi, we here analyze ciliated bronchial epithelium from individuals with acute KD by light microscopy (LM) and transmission electron microscopy (TEM) Individuals, Materials, and Methods family [8]. We used LM staining and TEM to determine whether intracytoplasmic inclusion body were present in acute KD bronchial epithelium and to determine whether, in addition to protein, nucleic acid was a component of the body (table 2) Open in a separate window Table 2 Results of experiments with acute Kawasaki disease (KD) ciliated bronchial epithelial cells and hematoxylin-eosinCstained sections from individuals 4 and 6 showing amphophilic spheroidal cytoplasmic inclusion body and irregular, golden yellow, granular, supranuclear pigment resembling classic lipofuscin Immunohistochemistry-stained section from patient 3 demonstrating brownish, spheroidal, cytoplasmic inclusion body identified with synthetic KD antibody J. Methylene blue/azure II/fundamental fuchsin trichromeCstained section from patient 2 showing dark blue cytoplasmic inclusion body; goblet cells FRAX1036 stained reddish. Initial magnifications, 640 for those panels Open in a separate window Number 2 Detection of antigen in inflamed, partially necrotic bronchus from patient 4. Hematoxylin-eosin stain of FRAX1036 bronchus. Most of the right side of the bronchus shows FRAX1036 swelling with.