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A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease
Abstract Background Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown....
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| Published in: | The Journal of infectious diseases 2020-06, Vol.222 (1), p.158-168 |
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| container_title | The Journal of infectious diseases |
| container_volume | 222 |
| creator | Rowley, Anne H Baker, Susan C Arrollo, David Gruen, Leah J Bodnar, Tetyana Innocentini, Nancy Hackbart, Matthew Cruz-Pulido, Yazmin E Wylie, Kristine M Kim, Kwang-Youn A Shulman, Stanford T |
| description | Abstract
Background
Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.
Methods
We isolated single peripheral blood plasmablasts from children with KD 1–3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.
Results
Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P |
| doi_str_mv | 10.1093/infdis/jiaa066 |
| format | article |
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Background
Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.
Methods
We isolated single peripheral blood plasmablasts from children with KD 1–3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.
Results
Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P < .01), recognized the KD peptide antigen.
Conclusions
These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.
We prepared monoclonal antibodies from plasmablasts from children with Kawasaki disease (KD). The antibodies recognize inclusion bodies in fatal KD tissues containing a specific protein epitope. KD sera from week 2 of illness but not infant control sera recognize the epitope.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiaa066</identifier><identifier>PMID: 32052021</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Aneurysm ; Aneurysms ; Antibodies, Monoclonal - genetics ; Antibodies, Monoclonal - immunology ; Antibody Formation - genetics ; Antibody response ; Antigens ; Blood Cells - immunology ; Children ; Coronary artery ; Coronary artery disease ; Epidemiology ; Epithelial cells ; Epitopes ; Epitopes - immunology ; Female ; Heart diseases ; Humans ; Inclusion bodies ; Infant ; Kawasaki disease ; Major and Brief Reports ; Male ; Monoclonal antibodies ; Mucocutaneous lymph node syndrome ; Mucocutaneous Lymph Node Syndrome - epidemiology ; Mucocutaneous Lymph Node Syndrome - genetics ; Mucocutaneous Lymph Node Syndrome - immunology ; Patients ; Pediatrics ; Peptides ; Peripheral blood ; United States - epidemiology</subject><ispartof>The Journal of infectious diseases, 2020-06, Vol.222 (1), p.158-168</ispartof><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-bf5b176a1a04115df98628928051c53ab9e07b27b848575ff55e6a3066dcb7c33</citedby><cites>FETCH-LOGICAL-c518t-bf5b176a1a04115df98628928051c53ab9e07b27b848575ff55e6a3066dcb7c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32052021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rowley, Anne H</creatorcontrib><creatorcontrib>Baker, Susan C</creatorcontrib><creatorcontrib>Arrollo, David</creatorcontrib><creatorcontrib>Gruen, Leah J</creatorcontrib><creatorcontrib>Bodnar, Tetyana</creatorcontrib><creatorcontrib>Innocentini, Nancy</creatorcontrib><creatorcontrib>Hackbart, Matthew</creatorcontrib><creatorcontrib>Cruz-Pulido, Yazmin E</creatorcontrib><creatorcontrib>Wylie, Kristine M</creatorcontrib><creatorcontrib>Kim, Kwang-Youn A</creatorcontrib><creatorcontrib>Shulman, Stanford T</creatorcontrib><title>A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Background
Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.
Methods
We isolated single peripheral blood plasmablasts from children with KD 1–3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.
Results
Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P < .01), recognized the KD peptide antigen.
Conclusions
These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.
We prepared monoclonal antibodies from plasmablasts from children with Kawasaki disease (KD). The antibodies recognize inclusion bodies in fatal KD tissues containing a specific protein epitope. KD sera from week 2 of illness but not infant control sera recognize the epitope.</description><subject>Aneurysm</subject><subject>Aneurysms</subject><subject>Antibodies, Monoclonal - genetics</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Formation - genetics</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Blood Cells - immunology</subject><subject>Children</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Epidemiology</subject><subject>Epithelial cells</subject><subject>Epitopes</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Inclusion bodies</subject><subject>Infant</subject><subject>Kawasaki disease</subject><subject>Major and Brief Reports</subject><subject>Male</subject><subject>Monoclonal antibodies</subject><subject>Mucocutaneous lymph node syndrome</subject><subject>Mucocutaneous Lymph Node Syndrome - epidemiology</subject><subject>Mucocutaneous Lymph Node Syndrome - genetics</subject><subject>Mucocutaneous Lymph Node Syndrome - immunology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Peptides</subject><subject>Peripheral blood</subject><subject>United States - epidemiology</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkT1PHDEQhq0oKFwgbcrIUppQLPhj_dVEOgEhCCQQgtqyd2fBl7v1xvaC7t9n0V0QSUM1xTzzal49CH2m5JASw49C37UhHy2Cc0TKd2hGBVeVlJS_RzNCGKuoNmYXfcx5QQipuVQf0C5nRDDC6AydzfF1igVCj0-HUOIA-NaleyjQYr_G5QHwvC_Bx3aNbyAPsc-AS8QX7sll9yvgk5DBZdhHO51bZvi0nXvo7sfp7fHP6vLq7Px4flk1gupS-U54qqSjjtSUirYzWjJtmCaCNoI7b4Aoz5TXtRZKdJ0QIB2fqrWNVw3ne-j7JncY_QraBvqS3NIOKaxcWtvogv1304cHex8frWJGakmmgG_bgBR_j5CLXYXcwHLpeohjtoyLWnFlDJvQr_-hizimfqpnWV1rqbmgz9ThhmpSzDlB9_IMJfbZkd04sltH08GX1xVe8L9SJuBgA8RxeCvsD8FGnKc</recordid><startdate>20200616</startdate><enddate>20200616</enddate><creator>Rowley, Anne H</creator><creator>Baker, Susan C</creator><creator>Arrollo, David</creator><creator>Gruen, Leah J</creator><creator>Bodnar, Tetyana</creator><creator>Innocentini, Nancy</creator><creator>Hackbart, Matthew</creator><creator>Cruz-Pulido, Yazmin E</creator><creator>Wylie, Kristine M</creator><creator>Kim, Kwang-Youn A</creator><creator>Shulman, Stanford T</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200616</creationdate><title>A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease</title><author>Rowley, Anne H ; Baker, Susan C ; Arrollo, David ; Gruen, Leah J ; Bodnar, Tetyana ; Innocentini, Nancy ; Hackbart, Matthew ; Cruz-Pulido, Yazmin E ; Wylie, Kristine M ; Kim, Kwang-Youn A ; Shulman, Stanford T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-bf5b176a1a04115df98628928051c53ab9e07b27b848575ff55e6a3066dcb7c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aneurysm</topic><topic>Aneurysms</topic><topic>Antibodies, Monoclonal - genetics</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Formation - genetics</topic><topic>Antibody response</topic><topic>Antigens</topic><topic>Blood Cells - immunology</topic><topic>Children</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Epidemiology</topic><topic>Epithelial cells</topic><topic>Epitopes</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Inclusion bodies</topic><topic>Infant</topic><topic>Kawasaki disease</topic><topic>Major and Brief Reports</topic><topic>Male</topic><topic>Monoclonal antibodies</topic><topic>Mucocutaneous lymph node syndrome</topic><topic>Mucocutaneous Lymph Node Syndrome - epidemiology</topic><topic>Mucocutaneous Lymph Node Syndrome - genetics</topic><topic>Mucocutaneous Lymph Node Syndrome - immunology</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Peptides</topic><topic>Peripheral blood</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rowley, Anne H</creatorcontrib><creatorcontrib>Baker, Susan C</creatorcontrib><creatorcontrib>Arrollo, David</creatorcontrib><creatorcontrib>Gruen, Leah J</creatorcontrib><creatorcontrib>Bodnar, Tetyana</creatorcontrib><creatorcontrib>Innocentini, Nancy</creatorcontrib><creatorcontrib>Hackbart, Matthew</creatorcontrib><creatorcontrib>Cruz-Pulido, Yazmin E</creatorcontrib><creatorcontrib>Wylie, Kristine M</creatorcontrib><creatorcontrib>Kim, Kwang-Youn A</creatorcontrib><creatorcontrib>Shulman, Stanford T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rowley, Anne H</au><au>Baker, Susan C</au><au>Arrollo, David</au><au>Gruen, Leah J</au><au>Bodnar, Tetyana</au><au>Innocentini, Nancy</au><au>Hackbart, Matthew</au><au>Cruz-Pulido, Yazmin E</au><au>Wylie, Kristine M</au><au>Kim, Kwang-Youn A</au><au>Shulman, Stanford T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2020-06-16</date><risdate>2020</risdate><volume>222</volume><issue>1</issue><spage>158</spage><epage>168</epage><pages>158-168</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract
Background
Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.
Methods
We isolated single peripheral blood plasmablasts from children with KD 1–3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.
Results
Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P < .01), recognized the KD peptide antigen.
Conclusions
These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.
We prepared monoclonal antibodies from plasmablasts from children with Kawasaki disease (KD). The antibodies recognize inclusion bodies in fatal KD tissues containing a specific protein epitope. KD sera from week 2 of illness but not infant control sera recognize the epitope.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32052021</pmid><doi>10.1093/infdis/jiaa066</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford Journals Online |
| subjects | Aneurysm Aneurysms Antibodies, Monoclonal - genetics Antibodies, Monoclonal - immunology Antibody Formation - genetics Antibody response Antigens Blood Cells - immunology Children Coronary artery Coronary artery disease Epidemiology Epithelial cells Epitopes Epitopes - immunology Female Heart diseases Humans Inclusion bodies Infant Kawasaki disease Major and Brief Reports Male Monoclonal antibodies Mucocutaneous lymph node syndrome Mucocutaneous Lymph Node Syndrome - epidemiology Mucocutaneous Lymph Node Syndrome - genetics Mucocutaneous Lymph Node Syndrome - immunology Patients Pediatrics Peptides Peripheral blood United States - epidemiology |
| title | A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease |
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