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Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease
Anne H Rowley1,2,3, Susan C Baker4, David Arrollo3
1Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Insights
Researchers identified a specific peptide antigen targeted by antibodies in children with Kawasaki disease (KD). This discovery offers a new way to understand the cause of this serious childhood heart condition.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Kawasaki disease (KD) is a primary cause of acquired heart disease in children, potentially leading to coronary artery aneurysms and fatalities.
- While infectious origins are suspected, the specific antigens triggering KD remain unidentified.
- Antibodies from peripheral blood plasmablasts in infected individuals are typically antigen-specific.
Purpose of the Study:
- To identify specific antigenic targets of the antibody response in Kawasaki disease.
- To develop diagnostic tools for KD by characterizing the serologic response to identified antigens.
Main Methods:
- Monoclonal antibodies (mAbs) were generated from peripheral blood plasmablasts of children with KD.
- mAbs were used to identify target antigens, including a specific peptide.
- Serologic responses to the identified KD peptide antigen were assessed in KD patients and control groups.
Main Results:
- Thirty-two mAbs recognized antigens within inclusion bodies in bronchial epithelial cells from fatal KD cases.
- Five mAbs, from patients with coronary aneurysms, identified a specific peptide blocking this binding.
- Sera from KD patients showed significantly higher recognition of the KD peptide antigen compared to infant controls.
Conclusions:
- A specific protein epitope targeted by the antibody response in Kawasaki disease has been identified.
- This finding provides a potential diagnostic marker and a pathway to understanding KD pathogenesis.
- The identified peptide antigen is crucial for elucidating the mechanisms behind this significant pediatric disease.
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.
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