News Release 

New study aims to better understand Kawasaki disease

Kawasaki disease is a childhood vasculitis, marked by prolonged fevers and coronary artery inflammation/aneurysms in near one-quarter of those untreated

Pediatric Academic Societies

BALTIMORE - A new study looks to define the antibody characteristics, including clonality, of plasmablasts during Kawasaki Disease (KD). Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

"We still don't know the cause of KD, the leading cause of childhood acquired heart disease in developed nations," said Mark Hicar, MD, PhD, one of the authors of the study. "During a normal infectious immune response, special B cells called plasmablasts that are specific to the infection are found in the peripheral blood. We are characterizing these responses in a number of children with KD, have created antibodies from these plasmablasts, and are using these to identify the cause of KD."

Researchers used antibody repertoire next-generation sequencing to characterize memory and PB populations. Additionally, pairing of heavy and light chains was performed with Chromium Single Cell Gene Expression (10x Genomics, Pleasanton, CA) using the Human B cell Single Cell V(D)J Enrichment Kit.

From plasmablasts from subject 24, antibody sequences using VH4-34 and a 19 amino acid length complementarity determining region 3 showed a massive expansion between day four and six of fever. Chromium single cell sequencing produced over 946 heavy and light chain paired sequences. Sequence comparison showed 40% of sequences demonstrated markers of clonal expansion, which represented 100 clonal groups. One clonal group (24-01) reflected the massive clonal expansion (VH4-34, CDR3 19) previously shown within the next-generation sequencing data.

This clonal expansion within plasmablast populations supports that KD is caused by an infection. Antigen targeting of monoclonal antibodies from these clones is currently being explored.

Dr. Hicar will present findings from "Clonal expansion within circulating plasmblast populations lends support for an infectious disease etiology of Kawasaki disease" on Monday, April 29 at 10:30 a.m. EDT. Reporters interested in an interview with Dr. Hicar should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

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About the Pediatric Academic Societies Meeting

The Pediatric Academic Societies (PAS) Meeting brings together thousands of pediatricians and other health care providers united by a common mission: to improve the health and well-being of children worldwide. This international gathering includes pediatric researchers, leaders in pediatric academics, clinical care providers and community practitioners. Presentations cover issues of interest to generalists as well as topics critical to a wide array of specialty and sub-specialty areas. The PAS Meeting will be the premier North American scholarly child health meeting. The PAS Meeting is produced through a partnership of four pediatric organizations that are leaders in the advancement of pediatric research and child advocacy: American Pediatric Society, Society for Pediatric Research, Academic Pediatric Association and American Academy of Pediatrics. For more information, please visit http://www.pas-meeting.org. Follow us on Twitter @PASMeeting and #PAS2019, and like us on Facebook.

Abstract: Clonal expansion within circulating plasmblast populations lends support for an infectious disease etiology of Kawasaki disease

Background: Kawasaki Disease (KD) is a childhood vasculitis, marked by prolonged fevers and coronary artery inflammation/aneurysms in near one quarter of those untreated. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. Plasmablasts (PBs) are a stage of transitional B-cells that lead to plasma cells, the long-lived antibody producing cells of the bone marrow. After initial infection, peripherally circulating PB populations are enriched for cells with antibodies against the preceding infection.

Objective: We have recently published data showing children with KD have similar PB responses to children with infections. We sought to define the antibody characteristics, including clonality, of these PBs during KD.

Design/Methods: We used antibody repertoire next-generation sequencing to characterize memory and PB populations. Additionally, pairing of heavy and light chains was performed with Chromium Single Cell Gene Expression (10x Genomics, Pleasanton, CA) using the Human B cell Single Cell V(D)J Enrichment Kit.

Results: From subject 24, antibody sequences using VH4-34 and a 19 amino acid length complementarity determining region 3 showed a massive expansion between day 4 and 6 of fever. Chromium single cell sequencing produced over 946 heavy and light chain paired sequences. Sequence comparison showed 40% of sequences demonstrated markers of clonal expansion, which represented 100 clonal groups. One clonal group (24-01) reflected the massive clonal expansion (VH4-34, CDR3 19) previously shown.

Conclusion(s): This clonal expansion within plasmablast populations supports that Kawasaki disease is caused by an infection. Antigen targeting of these monoclonal antibodies is currently being explored.

Authors: Sarah Baron, Hakimuddin Sojar, Mark Hicar

Authors/Institutions: S. Baron, H. Sojar, M. Hicar, Pediatrics, University at Buffalo, Buffalo, New York, UNITED STATES

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