Monoclonal Antibodies From Children With Acute Kawasaki Disease Identify a Common Antigenic Target in Fatal Cases Over 5 Decades

Abstract

Kawasaki disease (KD) is a unique febrile illness of young children that can result in coronary artery aneurysms, myocardial infarction, aneurysm rupture, and sudden death. The epidemiologic features, including the young age group affected, the rarity of recurrence, and the presence of epidemics and outbreaks, point to a single infectious causative agent. The recent decrease in KD cases worldwide during pandemic mitigation supports transmission of the agent via a respiratory route. However, substantial research over decades has shown that KD etiology cannot be linked to any currently known infectious agent. We previously identified the presence of intracytoplasmic inclusion (ICI) bodies in the bronchial epithelium in children with fatal KD and a convergent plasmablast-derived antibody response to a specific protein epitope, supporting 1 predominant respiratory causative agent. Here, we report immunohistochemistry and epitope binding using an expanded pool of KD monoclonal antibodies prepared from single peripheral blood plasmablasts from 12 children with acute KD. We identified 1 or more monoclonal antibodies from each of the 12 patients that recognized ICI bodies in KD bronchial epithelium. Using a representative monoclonal antibody, ICI bodies were detected in 20 of 20 children with fatal KD across 5 decades, 10 from the United States and 10 from Japan, and were absent in 19 of 20 infant controls (P < .001). We also found that all 12 children with acute KD generated plasmablast(s) recognizing the previously reported peptide antigen. Taken together, these results point to 1 predominant causative agent of KD across many decades and geographic areas and should direct future KD research studies.

Keywords: Kawasaki disease; antigen; inclusion bodies; medium-sized airways; monoclonal antibodies; plasmablasts.