Analysis of Plasmablasts From Children With Kawasaki Disease Reveals Evidence of a Convergent Antibody Response to a Specific Protein Epitope

Background Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. Methods We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. Results We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. Conclusions These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness. We analyzed plasmablasts from children with Kawasaki disease and identified a convergent VH3-74 antibody response with a shared CDR3 motif and directed at a single protein antigen, supporting one predominant causative agent in its pathogenesis.

Automated summary

Background: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. COVID-19 mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. Methods: Amino acid substitution scans were performed to develop modified peptides with improved recognition by KD monoclonal antibodies (MAbs). Results: A modified peptide epitope recognized by 20 MAbs from 11 KD patients was reported, suggesting a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD.