Work

B-cell receptor repertoire remodeling in Kawasaki disease is associated with clonal expansion and distinct repertoire features in coronary artery lesions

Year: 2026

Type: article

Abstract: Background: Kawasaki disease (KD) is an acute systemic vasculitis in children, but the characteristics of the B-cell receptor (BCR) repertoire during acute disease and their association with coronary artery lesions (CALs) remain poorly understood. Methods: High-throughput sequencing of BCR heavy-chain (BCR-H) CDR3 regions was performed in 22 children, including 9 healthy controls and 13 patients with KD, of whom 9 had no CAL and 4 had CAL. Repertoire diversity, clonal expansion, immunoglobulin isotype distribution, V-J gene usage, CDR3 characteristics, and inter-individual and cross-isotype repertoire sharing were systematically evaluated. Results: KD exhibited reduced BCR repertoire diversity, with a significant decrease in IgM diversity. The repertoire showed increased contributions of high-frequency and hyperexpanded clonotypes, with the most pronounced expansion in patients with CAL. IgM displayed the strongest clonal remodeling, characterized by reduced low-frequency and increased highly abundant clonotypes. KD also showed selective alterations in IGHV usage and V-J gene pairing. CAL was associated with increased IGHA usage and changes in CDR3 amino acid composition. Substantial inter-individual CDR3 sharing was observed among KD patients, and 20 recurrent clonotypes absent from healthy controls were identified as candidate KD-associated sequences. Cross-isotype CDR3 sharing also tended to be higher in KD, particularly among patients with CAL. Conclusions: Acute KD is characterized by substantial BCR repertoire remodeling, marked by selective IgM clonal expansion, repertoire convergence, and CAL-associated IgA-biased remodeling. These findings provide new insights into humoral immune dysregulation in KD and identify candidate B-cell clonotypes for further investigation of disease pathogenesis and coronary involvement.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1994376