Ultrastructural, Immunofluorescence, and RNA Evidence Support the Hypothesis of a 'New' Virus Associated With Kawasaki Disease
| Autor: | J. Carter Ralphe, Benjamin J. Soriano, Stanford T. Shulman, Julia H. Huang, Nuzhath F. Tajuddin, Kei Takahashi, Kenneth H. Rand, Jan M. Orenstein, Francesca L. Garcia, Susan C. Baker, Mitra B. Kalelkar, Simon Lin, Elizabeth J. Perlman, Jared M. Flatow, Linda M. Fox, Anne H. Rowley, Maria Tretiakova |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pathology medicine.medical_specialty Virosomes Cytoplasmic inclusion Fluorescent Antibody Technique Respiratory Mucosa Mucocutaneous Lymph Node Syndrome Biology Immunofluorescence Virus Inclusion bodies Inclusion Bodies Viral Major Articles and Brief Reports Microscopy Electron Transmission medicine Humans Immunology and Allergy Apical cytoplasm medicine.diagnostic_test Infant Newborn Infant Respiratory infection RNA Epithelial Cells Infectious Diseases Child Preschool Viruses biology.protein RNA Viral Female Antibody hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Infectious Diseases. 203:1021-1030 |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Kawasaki disease (KD) is a systemic vasculitis of young childhood that most significantly affects the coronary arteries. Although fatality rates are relatively low in countries attuned to the signs and symptoms and thus the diagnosis, the worldwide mortality and morbidity rates are unknown. Although the cause is unknown, clinical and epidemiologic data support the hypothesis of a ubiquitous etiologic agent that likely causes an inconsequential respiratory infection in the vast majority of children but disseminates and results in KD in a subset of children who are genetically predisposed [1]. An antigen-driven IgA immune response was detected in the walls of coronary and other arteries in the weeks following the onset of illness, leading to the hypothesis that the etiologic agent is microbial [2]. The beneficial or deleterious effect of the IgA antibodies remains to be ascertained. Synthetic versions of the IgA antibodies detect intracytoplasmic inclusion bodies (ICI) consistent with aggregates of viral protein and RNA in the apical region of ciliated epithelial cells of predominantly mid-sized bronchi of 85% of children with fatal KD, but not of infant controls [3–5]. With experience, the ICI can also be identified by light microscopy in hematoxylin-eosin stain sections. Cytoplasmic inclusions can be seen in a variety of virus and bacterial infections. They can also result from overproduced or misfolded aggregates of human proteins (ie, “aggresomes”[6]) in chronic neurodegenerative diseases such as Alzheimer's [7]. A primary feature of aggresomes is that they are surrounded by an intermediate filament “cage” [7]. Bacterial inclusion bodies contain bacterial forms that reflect their life cycle [8], in contrast to KD ICI, which are homogeneous. To determine whether the ICI seen in KD have a cage characteristic of an aggresome, we performed colocalization experiments using KD synthetic antibody plus an antibody to human cytokeratin, the intermediate filament present in bronchial epithelium [9]. To determine the nature of the RNAs in the apical cytoplasm of bronchial epithelium containing ICI, we performed laser-capture microdissection, isolated RNA, and synthesized and sequenced complementary DNA (cDNA) using high-throughput methods. We performed real-time reverse transcription–polymerase chain reaction (RT-PCR) for selected genes on lung RNA from KD patients and infant controls. We analyzed the bronchial epithelium of formalin-fixed, non–paraffin embedded lung tissue from autopsies of 3 KD patients by transmission electron microscopy (TEM) to determine if any microbial forms could be observed in specimens containing ICI. |
| Databáze: | OpenAIRE |
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