The new study identifies antigens targeted by antibody response of children with Kawasaki disease (KD). The findings will be presented during a meeting of the Pediatric Academic Societies (PAS) 2019, which will take place April 24 – May 1 in Baltimore.
"To identify antigens targeted by antibody response in children with KD, we identified plasmablasts that were clonally expanded in peripheral blood of 11 children with KD and produced monoclonal antibodies from these plasmablasts," said Anne Rowley, MD, one of the study's authors; studies. "Monoclonal antibodies from nine out of 11 patients identified intracytoplasmic inclusion bodies in ciliary bronchial epithelium of fatal cases of CD. The subset of these antibodies recognizes peptides from non-structural hepacivir protein and the optimized peptide blocked the binding of these antibodies to inclusion bodies, demonstrating the presence of hepacivirus-like protein in inclusion bodies. These results strongly suggest that the new human virus, closely related to hepaciviruses and the respiratory portal of entry, is etiologically related to CD.
The study isolated peripheral blood (PB) from KD children 1-3 weeks after the onset of fever and characterized by single-cell RT-PCR. It identified oligoclonal PB sets and highly mutated IgA PB and generated monoclonal antibodies from these PBs. She used monoclonal antibodies to evaluate KD tissue reactivity and a peptide group containing 29,939 peptides derived from 13,123 B cell epitopes of animal viruses listed in the immune epitope database and in the assay source.
The study sequenced 1,156 PBs from 11 KD patients and identified 44 sets of oligoclonal PB in these patients. It produced 61 monoclonal antibodies (Mab) from oligoclonal PB and IgA PB, which showed high levels of somatic mutation. Ten of these antibodies bind strongly to KD ICI and 23 bind weakly. The animal virus peptide array revealed that Mab KD4-2H4 (from KD4 patient), which strongly binds ICI, recognized many similar peptides from the non-structural hepacivir C protein with the identified motif, which was highly significant for e-118. Patient KD4 had a negative hepatitis C serology. Peptide substitution analysis was performed to identify optimal amino acids for binding of KD4-2H4 at each position. An optimized peptide ELISA revealed that four additional KD Mabs recognized this peptide from two other KD patients; all three patients had coronary aneurysms. Strong ICI binding of KD Mabs KD4-2H4 and KD6-2B2 was completely blocked by pre-incubation with optimized peptide.
Children with KD produce antibodies against hepacivirus peptides and KD ICIs contain a protein with an epitope similar to hepaciviruses. These results strongly suggest that the new human virus, closely related to hepaciviruses and the respiratory portal of entry, is etiologically related to KD. Identifying specific etiology of CD could revolutionize the diagnosis and treatment of CD.
Dr. Rowley will present results from "Monoclonal Antibodies from Children with Kawasaki Disease (KD) Recognize Hepatic Viruses" on Monday April 29 at 2:00 pm. EDT. Reporters Interested in Talking to Dr. Rowley, they should turn [email protected] Please note that only summaries are presented at the meeting. In some cases, researchers may have additional data to share with the media.
PAS 2019 brings together thousands of pediatricians and other healthcare providers to improve the health and well-being of children around the world.