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406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses

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...

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Autores principales: Baron, Sarah, Sojar, Hakimuddin T, Hicar, Mark D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810807/
http://dx.doi.org/10.1093/ofid/ofz360.479
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author Baron, Sarah
Sojar, Hakimuddin T
Hicar, Mark D
author_facet Baron, Sarah
Sojar, Hakimuddin T
Hicar, Mark D
author_sort Baron, Sarah
collection PubMed
description 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. 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. 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. Seven other KD subjects are being processed and comparative analysis will be presented. CONCLUSION: 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. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68108072019-10-28 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses Baron, Sarah Sojar, Hakimuddin T Hicar, Mark D Open Forum Infect Dis Abstracts 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. 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. 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. Seven other KD subjects are being processed and comparative analysis will be presented. CONCLUSION: 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. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6810807/ http://dx.doi.org/10.1093/ofid/ofz360.479 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Baron, Sarah
Sojar, Hakimuddin T
Hicar, Mark D
406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title_full 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title_fullStr 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title_full_unstemmed 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title_short 406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
title_sort 406. cloning antibodies against kawasaki disease from acute plasmablast responses
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810807/
http://dx.doi.org/10.1093/ofid/ofz360.479
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