Tracking Immune Response Identifies Kawasaki Disease Agent

A new study identifies antigens targeted by the antibody response of children with Kawasaki Disease (KD), an inflammatory disease of previously unknown origin that can cause fever and rash. The presentation "Monoclonal Antibodies from Children with Kawasaki Disease (KD) Recognize Hepacivirus Peptides" was held today during the Pediatric Academic Societies (PAS) 2019 Meeting.

For the study, peripheral blood was isolated from 11 children with KD 1-3 weeks after fever onset. Using RT-PCR to characterize antibody response, specific immunoglobulin sets were identified along with highly mutated IgA peripheral blood; monoclonal antibodies were generated from these sets. Monoclonal antibodies were then evaluated for their reactivity to KD tissues and to a peptide array comprising tens of thousands of peptides from B cell epitopes of animal viruses in the Immune Epitope Database and Analysis Resource.

The peptide array revealed that Mab KD4-2H4, which strongly binds KD ICI recognizes multiple similar peptides from a nonstructural protein of hepacivirus C in one patient, KD4, in spite of a negative hepatitis C serology in the patient. Using ELISA testing, four other KD mAbs from two additional KD patients were also found to recognize this patient. All three patients had coronary aneurysims.

The observation that children with KD make antibodies to hepacivirus peptides and KD ICI contains a protein with a hepacivirus-like epitope suggests that a new human virus, closely related to the hepaciviruses, with a respiratory route of entry, is related to KD. Identification of the specific origin of KD could change the way KD is diagnosed and treated in the future.