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1.
J Infect Dis ; 222(1): 158-168, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32052021

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.


Subject(s)
Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , Antibody Formation/genetics , Blood Cells/immunology , Epitopes/immunology , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/immunology , Female , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/epidemiology , United States/epidemiology
2.
J Pediatric Infect Dis Soc ; 6(4): 386-388, 2017 Nov 24.
Article in English | MEDLINE | ID: mdl-28177492

ABSTRACT

Kawasaki disease (KD) shock syndrome (KDSS) is hypotension with KD. We compared children with KDSS and matched control children with KD. Children with KDSS more often were female, had a lower platelet count and sodium concentration, had a condition refractory to immunoglobulin, and had abnormal echocardiography results. KDSS is a unique subset of KD.


Subject(s)
Hyponatremia/etiology , Mucocutaneous Lymph Node Syndrome/complications , Case-Control Studies , Child, Preschool , Echocardiography , Female , Humans , Hypotension/etiology , Male , Organoplatinum Compounds , Sodium/blood
3.
Pediatr Infect Dis J ; 33(12): 1296-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25037038

ABSTRACT

We hypothesized that cardiovascular miRNAs might be diagnostic biomarkers for Kawasaki disease (KD). We identified dysregulated miRNAs in KD coronary arteries, and tested sera from KD patients and febrile controls for cardiovascular miRNAs using 2 methods. We did not identify cardiovascular miRNAs diagnostic for KD; our results may help guide future studies of potential miRNA biomarkers for KD.


Subject(s)
Biomarkers/analysis , Biomarkers/blood , Coronary Vessels/pathology , MicroRNAs/analysis , MicroRNAs/blood , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/pathology , Child , Female , Humans , Infant , Infant, Newborn , Male
4.
Pediatrics ; 125(2): e234-41, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20100771

ABSTRACT

OBJECTIVE: The 2004 American Heart Association (AHA) statement included a clinical case definition and an algorithm for diagnosing and treating suspected incomplete Kawasaki disease (KD). We explored the performance of these recommendations in a multicenter series of US patients with KD with coronary artery aneurysms (CAAs). METHODS: We reviewed retrospectively records of patients with KD with CAAs at 4 US centers from 1981 to 2006. CAAs were defined on the basis of z scores of >3 or Japanese Ministry of Health and Welfare criteria. Our primary outcome was the proportion of patients presenting at illness day < or =21 who would have received intravenous immunoglobulin (IVIG) treatment by following the AHA guidelines at the time of their initial presentation to the clinical center. RESULTS: Of 195 patients who met entry criteria, 137 (70%) met the case definition and would have received IVIG treatment at presentation. Fifty-three patients (27%) had suspected incomplete KD and were eligible for algorithm application; all would have received IVIG treatment at presentation. Of the remaining 5 patients, 3 were excluded from the algorithm because of fever for <5 days at presentation and 2 because of <2 clinical criteria at >6 months of age. Two of these 5 patients would have entered the algorithm and received IVIG treatment after follow-up monitoring. Overall, application of the AHA algorithm would have referred > or =190 patients (97%) for IVIG treatment. CONCLUSIONS: Application of the 2004 AHA recommendations, compared with the classic criteria alone, improves the rate of IVIG treatment for patients with KD who develop CAAs. Future multicenter prospective studies are needed to assess the performance characteristics of the AHA algorithm in febrile children with incomplete criterion findings and to refine the algorithm further.


Subject(s)
Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/therapy , Adolescent , Algorithms , Child , Child, Preschool , Coronary Aneurysm/etiology , Female , Humans , Infant , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/complications , Practice Guidelines as Topic , Young Adult
5.
Epidemiology ; 20(2): 194-201, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19129731

ABSTRACT

BACKGROUND: : Kawasaki disease exhibits a distinct seasonality, and short-term changes in weather may affect its occurrence. METHODS: : To investigate the effects of weather variability on the occurrence of this syndrome, we conducted a time-between-events analysis of consecutive admissions for Kawasaki disease to a large pediatric hospital in Chicago. We used gamma regression to model the times between admissions. This is a novel application of gamma regression to model the time between admissions as a function of subject-specific covariates. RESULTS: : We recorded 723 admissions in the 18-year (1986-2003) study period, of which 700 had complete data for analysis. Admissions for Kawasaki disease in Chicago were seasonal: The mean time between admissions was 34% shorter (relative time = 0.66, 95% confidence interval 0.54-0.81) from January-March than from July-September. In 1998, we recorded a larger number of admissions for Kawasaki disease (n = 65) than in other years (mean n = 37). January-March months of 1998 were warmer by a mean of 3 degrees C (1.5 degrees C-4.4 degrees C) and the mean time between admissions was 48% shorter (relative time = 0.52, 0.36-0.75) than in equivalent periods of other study years. CONCLUSIONS: : Our findings show that atypical changes in weather affect the occurrence of Kawasaki disease and are compatible with a link to an infectious trigger. The analysis of interevent times using gamma regression is an alternative to Poisson regression in modeling a time series of sparse daily counts.


Subject(s)
Hospitalization/trends , Mucocutaneous Lymph Node Syndrome/epidemiology , Weather , Chicago/epidemiology , Hospitals, Pediatric , Humans , Medical Audit , Poisson Distribution , Retrospective Studies
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