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BALTIMORE – A new study seeks to define the characteristics of antibodies, including clonality, of plasmablasts during Kawasaki disease (KD). The results of the study will be presented at the Pediatric Academic Societies (PAS) 2019 meeting, which will take place from April 24 to May 1 in Baltimore.
"We still do not know the cause of KD, the leading cause of acquired heart disease in children in developed countries," said Mark Hicar, MD, PhD, one of the authors of the study. ;study. "During a normal infectious immune response, special B cells, called plasmablasts, specific to infection are found in the peripheral blood.We characterize these responses in a number of children with KD, we created antibodies from these plasmablasts and use them to identify the cause of KD. "
The researchers used next generation sequencing of the antibody repertoire to characterize memory and PB populations. In addition, heavy and light chain pairing was performed with the expression of the single cell chromium gene (10x Genomics, Pleasanton, CA) using the single enrichment kit. V (D) J cell with human B cells.
From the subject's plasmablasts 24, the antibody sequences using VH4-34 and a complementarity determining region of length 19 amino acids 3 showed a mbadive expansion between the fourth and sixth day of fever. Chromium single cell sequencing produced more than 946 heavy and light chain paired sequences. Sequence comparison showed that 40% of the sequences showed markers of clonal expansion, which represented 100 clonal groups. A clonal group (24-01) reflected the clonal exponential expansion (VH4-34, CDR3 19) previously shown in the next generation sequencing data.
This clonal expansion within plasmablast populations confirms that KD is caused by infection. The antigenic targeting of the monoclonal antibodies of these clones is being explored.
Dr. Hicar will present the results of "Clonal Expansion in Circulating Plasmblast Populations Provides Support for the Aetiology of an Infectious Disease of Kawasaki Disease" on Monday, April 29 at 10:30 am Eastern Daylight Saving Time. Journalists interested in an interview with Dr. Hicar should contact [email protected]. Please note that only abstracts are presented at the meeting. In some cases, researchers may have additional data to share with the media.
The PAS 2019 meeting brings together thousands of pediatricians and other health care providers with the goal of improving the health and well-being of children around the world. For more information on the PAS 2019 meeting, go to http: // www.
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About the University Pediatric Society Meeting
The meeting of the Pediatric University Societies (PAS) brings together thousands of pediatricians and other health professionals united by a common mission: to improve the health and well-being of children around the world. This international gathering includes pediatric researchers, pediatric academic leaders, clinical care providers and community practitioners. The presentations cover topics of interest to generalists as well as critical topics for a wide range of specialty and subspecialty areas. The SSP meeting will be the first North American scholarly meeting on children's health. The PAS meeting is the result of a partnership between four pediatric organizations that play a leading role in promoting pediatric research and advocating for children's rights: American Pediatric Society, Pediatric Research Society, University Association of Pediatrics and American Academy of Pediatrics. For more information, please visit http: // www.
Abstract: Clonal expansion within circulating plasmblast populations provides support for the etiology of an infectious disease of Kawasaki disease
Context: Kawasaki disease (KD) is an infantile vasculitis characterized by prolonged fevers and coronary artery inflammation / aneurysm in nearly one-quarter of untreated patients. The cause remains unknown. However, epidemiological and demographic data confirm that only one previous infectious agent can result in MK. Plasmablasts (PBs) are a transient B-cell stage that lead to plasma cells, long-lived antibody-producing bone marrow cells. After initial infection, peripheral circulating PB populations are enriched in cells containing antibodies against the previous infection.
Goal: We recently published data showing that children with MK had PB responses similar to those of infected children. We sought to define the characteristics of antibodies, including clonality, of these PBs during KD.
Design / Methods: We used next generation sequencing of the antibody repertoire to characterize memory and PB populations. In addition, heavy and light chain pairing was performed with the expression of the single cell chromium gene (10x Genomics, Pleasanton, CA) using the single enrichment kit. V (D) J cell with human B cells.
Results: According to subject 24, antibody sequences using VH4-34 and a 19-amino acid length-matching region 3 showed a mbadive expansion between day 4 and day 6 of fever. Chromium single cell sequencing produced more than 946 heavy and light chain paired sequences. Sequence comparison showed that 40% of the sequences showed markers of clonal expansion, which represented 100 clonal groups. A clonal group (24-01) reflected the mbadive clonal development (VH4-34, CDR3 19) presented previously.
Conclusion (s): This clonal expansion within plasmablast populations confirms that Kawasaki disease is caused by infection. The antigenic targeting of these monoclonal antibodies is currently under study.
authors: Sarah Baron, Hakimuddin Sojar, Mark Hicar
Authors / Institutions: S. Baron, H. Sojar, M. Hicar, Pediatrics, University of Buffalo, Buffalo, New York, USA
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