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BALTIMORE – New study identifies antigens targeted by the antibody response of children with Kawasaki Disease (KD). The results will be presented at the 2019 Pediatric Academic Societies (PAS) meeting, which will take place from April 24 to May 1 in Baltimore.
"To identify the antigens targeted by the antibody response of children with KD, we have identified plasmablasts that have clonally grown in the peripheral blood of 11 children with KD and manufactured monoclonal antibodies from these plasmablasts" , said Anne Rowley, MD, one of the authors of the study. "The monoclonal antibodies of nine of the 11 patients identified intracytoplasmic inclusion bodies in the ciliated bronchial epithelium of fatal KD cases.A subset of these antibodies recognizes the peptides of a non-protein. Hepatitis B, and an optimized peptide blocked the binding of these antibodies to the inclusion bodies, demonstrating the presence of a hepatitis-like protein in the inclusion bodies. These results strongly suggest that a new human virus, closely related to hepacivirus and endowed with a respiratory entry point, is etiologically related to KD. "
The study isolated the peripheral blood (PB) of children KD 1 to 3 weeks after the onset of fever and characterized the response with the help of a unicellular RT-PCR. He identified sets of oligoclonal PBs and a highly mutated IgA PB, and generated monoclonal antibodies from these PBs. He used monoclonal antibodies to evaluate reactivity to KD tissues and a set of peptides comprising 29,939 peptides derived from 13,123 animal B cell virus epitopes, described in the immune database of epitopes and resource. # 39; s badysis.
The study sequenced 1,156 PB from 11 KD patients and identified 44 sets of oligoclonal PB in these patients. He prepared 61 monoclonal antibodies (Mabs) from oligoclonal PBs and IgA PBs with high levels of somatic mutation. Ten of these antibodies bind strongly to KD ICI and 23 bind weakly. The peptide matrix of the animal virus revealed that Mab KD4-2H4 (from patient KD4), which binds strongly to ICI, recognized multiple similar peptides of a nonstructural protein of hepatitis C with a pattern identified highly significant at e-118. The KD4 patient had a negative hepatitis C serology. Peptide substitution badysis was performed to identify the optimal amino acids for KD4-2H4 binding at each position. An ELISA badysis using an optimized peptide revealed that four other Kabs from two other KD patients also recognized this peptide; all three patients had coronary aneurysms. The strong ICI binding of KD Mabs KD4-2H4 and KD6-2B2 was completely blocked by preincubation with the optimized peptide.
Children with KD make antibodies against peptides of the hepacivirus and KD ICI contains proteins with a hepatitis-like epitope. These results strongly suggest that a new human virus, closely related to hepacivirus and having a respiratory portal of entry, is etiologically related to KD. The identification of the specific etiology of KD could revolutionize the diagnosis and treatment of KD in the future.
Dr. Rowley will present the results of "Monoclonal Antibodies from Children with Kawasaki Disease (KD) Recognize Hepatitis Peptides" on Monday, April 29 at 2 pm EDT. Journalists interested in an interview with Dr. Rowley 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: Monoclonal antibodies of children with Kawasaki disease (KD) recognize the peptides of the hepacivirus
Context: We previously reported a plasma response of oligoclonal IgA plasma cells in KD arteries and made antibodies using oligoclonal immunoglobulin alpha heavy chains with random light chains. These antibodies identified immunohistochemistry in the ciliated bronchial epithelium of KD in intracytoplasmic inclusion bodies (ICI), but were unable to identify specific antigen, probably because They did not have adequate in vivo heavy and light chain partners correct. The badysis of peripheral blood plasmablasts (PB) has become a powerful tool for studying the response of antibodies to infectious diseases, and single-cell approaches allow the identification of heavy and light chains. related in each PB.
Goal: Identify antigens targeted by the antibody response of children with KD.
Design / Methods: We isolated PB from children with KD 1 to 3 weeks after the onset of fever and characterized the response by unicellular RT-PCR. We identified oligoclonal PB pools and highly mutated IgA PB, and generated monoclonal antibodies from these PBs. We used monoclonal antibodies to evaluate reactivity to KD tissues and a set of peptides comprising 29,939 peptides derived from 13,123 B epitopes of animal virus viruses reported in the database and resources for epitope immune badysis (http: // www.
Results: We sequenced 1156 PBs from 11 KD patients and identified 44 sets of oligoclonal PBs in these patients. We prepared 61 monoclonal antibodies (Mab) from oligoclonal PBs and IgA PBs with high levels of somatic mutation. Ten of these antibodies bind strongly to KD ICI and 23 bind weakly. The peptide matrix of the animal virus revealed that Mab KD4-2H4 (from patient KD4), which binds strongly to ICI, recognized multiple similar peptides of a nonstructural protein of hepatitis C with a pattern identified highly significant at e-118. The KD4 patient had a negative hepatitis C serology. Peptide substitution badysis was performed to identify the optimal amino acids for KD4-2H4 binding at each position. An ELISA badysis using an optimized peptide revealed that 4 other Kabs from two other KD patients also recognized this peptide; all three patients had coronary aneurysms. The strong ICI binding of KD Mabs KD4-2H4 and KD6-2B2 was completely blocked by preincubation with the optimized peptide.
Conclusion (s): Children with KD make antibodies against peptides of the hepacivirus and KD ICI contains proteins with a hepatitis-like epitope. These results strongly suggest that a new human virus, closely related to hepacivirus and having a respiratory portal of entry, is etiologically related to KD.
authors: Anne Rowley, Susan Baker, David Arrollo, Leah Gruen, Tetyana Bodnar, Nancy Innocentini, Stanford Shulman
Authors / Institutions: AH Rowley, D. Arrollo, LJ Gruen, T. Bodnar, N. Innocentini, ST Shulman, Pediatrics, Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA UNIS | Baker, Chicago Stritch School of Medicine, Loyola University, Chicago, Illinois, USA
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