ABSTRACT
BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. COVID mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. METHODS: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. RESULTS: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common CDR3 motif. CONCLUSIONS: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness.
Subject(s)
COVID-19 , Communicable Diseases , Child , Humans , Infectious Disease Medicine , SARS-CoV-2Subject(s)
Betacoronavirus/metabolism , Critical Care , Pandemics , Systemic Inflammatory Response Syndrome , COVID-19 , Child , Europe/epidemiology , Humans , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/metabolism , Mucocutaneous Lymph Node Syndrome/therapy , SARS-CoV-2 , Shock, Septic/diagnosis , Shock, Septic/epidemiology , Shock, Septic/metabolism , Shock, Septic/therapy , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/therapyABSTRACT
Department of Pediatrics, New York University (NYU) Winthrop Hospital, and professor of Pediatrics at NYU Long Island School of Medicine, Mineola, New York. Since the first report of an outbreak of respiratory disease in Wuhan, China, in December 2019 caused by a novel coronavirus (SARS CoV2), coronavirus disease (COVID-19) has reached pandemic proportions. The Centers for Disease Control and Prevention (CDC) established the following definition for MIS-C:3 * An individual aged 21 years and younger with fever for 1 or more days, laboratory evidence of inflammation, and illness requiring hospitalization with multisystem (2 or more) organ involvement (cardiac, renal, hematologic, gastrointestinal, dermatologic, neurologic), AND * No alternative plausible diagnosis, AND * Evidence of current or recent SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR), serology or antigen test, or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms. Ripha-gen and colleagues described 8 previously healthy children aged 4 to 14 years from Evelina London Children's Hospital who presented with hyperinflammatory shock and features similar to atypical Kawasaki disease (KD), KD shock syndrome (KDSS), or toxic shock syndrome (TSS) in mid-April 2020.4 Of the 8 cases, 6 were children of African-Caribbean descent, most were teenagers, and 5 were males. A series of 10 children aged 3 to 16 years (mostly teenagers) from Bergamo, Italy, presenting between February 18 and April 20, 2020, with what the authors labeled as severe Kawasaki-like disease was published in the Lancet on May 13, 2020.5 By definition, these children met the 2017 American Heart Association criteria for KD or incomplete KD with 5 or more days of fever, compatible rash, and mucous membrane findings, but the overall picture was not consistent with classic KD.