A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease

A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease:

Abstract

Background

Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause, but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are ~70% antigen-specific 1-2 weeks after infection.

Methods

We isolated single peripheral blood plasmablasts from children with KD at 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.

Results

Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to the inclusion bodies. Sera from 5/8 KD patients at day >8 after illness onset, compared with 0/17 infant controls (p<0.01), recognized the KD peptide antigen.

Conclusions

These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.