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. 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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Kawasaki disease

Challenging Concepts in Congenital and Acquired Heart Disease in the Young ◽

10.1093/med/9780198759447.003.0022 ◽

2020 ◽

pp. 291-302

Author(s):

Tarek Alsaied ◽

Justin T Tretter ◽

Andrew N Redington

Keyword(s):

Kawasaki Disease ◽

Treatment Options ◽

Significant Risk ◽

Developed Countries ◽

Coronary Imaging ◽

Coronary Aneurysms ◽

Acquired Heart Disease ◽

Immunoglobulin Treatment ◽

Long Term Prognosis

Kawasaki disease is the most common acquired heart disease in children in developed countries. Coronary involvement is reported in 30% of patients with no treatment and decreases to 5% with intravenous immunoglobulin treatment. Given the significant risk for coronary involvement, understanding the long-term prognosis is paramount to guide outpatient follow-up and treatment. This chapter presents the case of a 20-month-old child with Kawasaki disease and giant coronary aneurysms. The chapter reviews the diagnostic criteria and coronary imaging aspects, delves into the treatment options and prognosis, including immunoglobulin treatment.

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Incomplete Kawasaki Disease: What Can We Do About It?

Acta Medica Transilvanica ◽

10.2478/amtsb-2020-0074 ◽

2020 ◽

Vol 25 (4) ◽

pp. 57-59

Author(s):

Luminiţa Dobrotă ◽

Corina Cazan ◽

Dan-Vladimir Bratu ◽

Bogdan Neamţu

Keyword(s):

Heart Disease ◽

Kawasaki Disease ◽

Inflammatory Process ◽

Rare Condition ◽

Incomplete Kawasaki Disease ◽

Common Cause ◽

Surgical Interventions ◽

Coronary Aneurysms ◽

Acquired Heart Disease ◽

The Right

Abstract Kawasaki disease is a rare condition that mainly affects children younger than 6 years old. However, it represents the most common cause of acquired heart disease and the second most frequent vasculitis in children. Its importance consists in cardiac (coronary) complications identified in adults younger than 40 years old. Early diagnosis is pivotal for preventing (or reducing) coronary aneurysms and avoiding, at least, later unnecessary surgical interventions. Full (classic, complete) Kawasaki disease is easily diagnosed, even if the symptoms are not always present at the same time and most of them are unspecific. Incomplete Kawasaki disease implies challenge, delay or misdiagnosis. “Picking it up early is a winner” – the specialists say, so that early treatment administered at the right moment can stop the inflammatory process leading to much better outcomes, consequently.

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1876. A Hepacivirus-Like Protein Is Targeted by the Antibody Response to Kawasaki Disease (KD)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.106 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S48-S48

Author(s):

Anne Rowley ◽

Susan Baker ◽

David Arrollo ◽

Leah Gruen ◽

Bodnar Tetyana ◽

...

Keyword(s):

Inclusion Bodies ◽

Nonstructural Protein ◽

Infectious Agent ◽

Bronchial Epithelium ◽

Fourth Generation ◽

Single Patient ◽

Glutathione S Transferase ◽

Coronary Aneurysms ◽

Intracytoplasmic Inclusion Bodies ◽

Portal Of Entry

Abstract Background Clinical and epidemiologic data support a viral cause of KD, but the etiology has eluded 50 years of study. We previously identified virus-like intracytoplasmic inclusion bodies (ICI) in ciliated bronchial epithelium of KD children but not infant controls, but the antigens within the ICI were unknown. At 1–2 weeks following infection, 75% of peripheral blood plasmablasts (PB) specifically target the infectious agent. We cloned the PB response to KD to identify KD-specific antibodies and their target antigens. Methods We isolated single PB from children with KD 1–3 weeks after fever onset by flow cytometry, and amplified immunoglobulin VDJ and VJ genes from each PB by RT-PCR. We sequenced the products and made monoclonal antibodies (Mab) from clonally expanded PB in individual patients. Mab were tested for binding to KD tissues and to a viral peptide array containing 29,939 peptides from known B cell epitopes of animal viruses (www.iedb.org). Results We sequenced 1156 PB from 11 KD patients, and identified 44 clonally expanded sets of PB. We prepared 61 Mab from clonally expanded and highly mutated IgA PB, and found that 33/61 bind to KD ICI, 10 strongly and 23 weakly. Of 10 Mab that strongly bind, 2 were VH3-33 (single patient), 2 VH3-23 (single patient), 1 VH3-15, 1 VH3-74, 3 VH1-46 (2 patients), and 1 VH4-59. These Mab CDR3s varied from 11 to 20 aacids, with 4–28 aacid mutations. Mab KD4-2H4 recognized multiple similar peptides from nonstructural protein 4A of hepacivirus C; pt KD4 sera was negative for hepatitis C by fourth-generation ELISA. Amino acid substitution analysis yielded an optimized peptide, and 6 KD Mab recognized this peptide by ELISA. These 6 Mab derived from 3 KD patients, all of whom had coronary aneurysms, and were VH3-74 (n = 1), VH3-33 (n = 2, single patient), VH1-45 (n = 1), and VH3-72 (n = 2, single patient). Strong binding of KD Mab KD4-2H4 and KD6-2B2 to ICI was totally blocked by pre-incubation with optimized peptide. KD but not control sera react with optimized peptide expressed as a glutathione S-transferase fusion protein by western blot. Conclusion Children with KD make antibodies to a hepacivirus-like protein, and KD ICI contain this protein. These results strongly suggest that a previously unidentified hepacivirus with a respiratory portal of entry is etiologically related to KD. Disclosures All Authors: No reported Disclosures.

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Variation in the management of Kawasaki disease

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-317191 ◽

2019 ◽

Vol 105 (10) ◽

pp. 1004-1006 ◽

Cited By ~ 2

Author(s):

Audrey Dionne ◽

David Burgner ◽

Sarah De Ferranti ◽

Davinder Singh-Grewal ◽

Jane Newburger ◽

...

Keyword(s):

Kawasaki Disease ◽

Initial Treatment ◽

Coronary Aneurysm ◽

Medical Specialty ◽

Primary Treatment ◽

Management Options ◽

Necrosis Factor Alpha ◽

Coronary Aneurysms ◽

Factor Alpha ◽

Collaborative Efforts

Intravenous immunoglobulin (IVIG) reduces coronary aneurysms in patients with Kawasaki disease (KD), but additional management options remain challenging, with no generalisable evidence-based recommendations. We performed a survey of 724 physicians from 73 countries to assess variation in practice. IVIG was the preferred initial treatment by 659 (91%) of respondents. Criteria for adjunctive primary treatment varied considerably and definitions of IVIG resistance varied markedly by geographical continent, Human Development Index tiers and medical specialty. A second dose of IVIG was used most often for patients with coronary aneurysm non-responsive to initial treatment (572, 79%), but corticosteroids (379, 52%) and tumour necrosis factor alpha inhibitors (208, 29%) were also frequently used. Our findings highlight the need for international collaborative efforts to optimise management of patients with KD worldwide.

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Incomplete Kawasaki disease - a diagnostic and therapeutic challenge

Journal of College of Medical Sciences-Nepal ◽

10.3126/jcmsn.v9i4.10234 ◽

2014 ◽

Vol 9 (4) ◽

pp. 30-35

Author(s):

S Datta ◽

S Maiti ◽

G Das ◽

A Chatterjee ◽

P Ghosh

Keyword(s):

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Incomplete Kawasaki Disease ◽

Duration Of Symptoms ◽

Clinical Criteria ◽

Echocardiographic Finding ◽

2D Echocardiography ◽

Acquired Heart Disease ◽

The Mean ◽

One Year

Background The diagnosis of classical Kawasaki Disease was based on clinical criteria. The conventional criteria is particularly useful in preventing over diagnosis, but at the same time it may result in failure to recognize the incomplete form of Kawasaki Disease. Objective To suspect incomplete Kawasaki Disease, because early diagnosis and proper treatment may reduce substantial risk of developing coronary artery abnormality which is one of the leading causes of acquired heart disease in children. Method Nine cases of incomplete Kawasaki Disease were diagnosed over a period of one year. The diagnosis of incomplete Kawasaki Disease was based on fever for five days with less than four classical clinical features and cardiac abnormality detected by 2D- echocardiography. A repeat echocardiography was done after 6 weeks of onset of illness. The patients were treated with Intravenous Immunoglobulin and/or aspirin. Result The mean age of the patients was 3.83 years and the mean duration of symptoms before diagnosis was 12.1 days. Apart from other criteria all of our patients had edema and extreme irritability. All the patients had abnormal echocardiographic finding. Five patients received only aspirin due to nonaffordability of Intravenous Immunoglobulin and four patients received both aspirin and Intravenous Immunoglobulin, but the outcome was excellent in all the cases. Conclusion Incomplete Kawasaki Disease can be diagnosed with more awareness and aspirin alone may be used as a second line therapy in case of non affordability of Intravenous Immunoglobulin. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-4, 30-35 DOI: http://dx.doi.org/10.3126/jcmsn.v9i4.10234

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An update on the epidemiology, length of stay, and cost of Kawasaki disease hospitalisation in the United States

Cardiology in the Young ◽

10.1017/s1047951119000982 ◽

2019 ◽

Vol 29 (06) ◽

pp. 828-832 ◽

Cited By ~ 2

Author(s):

Laxmi V. Ghimire ◽

Fu-Sheng Chou ◽

Narayan B. Mahotra ◽

Sharan P. Sharma

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Length Of Stay ◽

Coronary Artery Aneurysm ◽

Artery Aneurysm ◽

Developed Countries ◽

The United States ◽

Hospital Charge ◽

Acquired Heart Disease ◽

The Developed Countries

AbstractBackground:Kawasaki disease is an acute vasculitis of childhood and is the leading cause of acquired heart disease in the developed countries.Methods:Data from hospital discharge records were obtained from the National Kids Inpatient Database for years 2009 and 2012. Hospitalisations by months, hospital regions, timing of admission, insurance types, and ethnicity were analysed. Length of stay and total charges were also analysed.Results:There were 10,486 cases of Kawasaki disease from 12,678,005 children hospitalisation. Kawasaki disease was more common between 0 and 5 years old, in male, and in Asian. The January–March quarter had the highest rate compared to the lowest in the July–September quarter (OR=1.62, p < 0.001). Admissions on the weekend had longer length of stay [4.1 days (95 % CI: 3.97–4.31)] as compared to admissions on a weekday [3.72 days (95 % CI: 3.64–3.80), p < 0.001]. Blacks had the longest length of stay and whites had the shortest [4.33 days (95 % CI: 4.12–4.54 days) versus 3.60 days (95 % CI: 3.48–3.72 days), p < 0.001]. Coronary artery aneurysm was identified in 2.7 % of all patients with Kawasaki disease. Children with coronary artery aneurysm were hospitalised longer and had higher hospital charge. Age, admission during weekend, and the presence of coronary artery aneurysm had significant effect on the length of stay.Conclusions:This report provides the most updated epidemiological information on Kawasaki disease hospitalisation. Age, admissions during weekend, and the presence of coronary artery aneurysm are significant contributors to the length of stay.

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Reduction of peripheral blood macrophages/monocytes in Kawasaki disease by intravenous gammaglobulin

European Journal of Pediatrics ◽

10.1007/bf01959479 ◽

1990 ◽

Vol 150 (1) ◽

pp. 43-47 ◽

Cited By ~ 11

Author(s):

S. Furukawa ◽

T. Matsubara ◽

K. Jujoh ◽

K. Sasai ◽

S. Nakachi ◽

...

Keyword(s):

Kawasaki Disease ◽

Peripheral Blood ◽

Intravenous Gammaglobulin

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Kawasaki disease complicated by cerebral infarction

Cardiology in the Young ◽

10.1017/s1047951103000179 ◽

2003 ◽

Vol 13 (1) ◽

pp. 103-105 ◽

Cited By ~ 14

Author(s):

Kenji Suda ◽

Masahiko Matsumura ◽

Shigeru Ohta

Keyword(s):

Kawasaki Disease ◽

Cerebral Infarction ◽

Clinical Situation ◽

Sudden Onset ◽

X Ray ◽

Coronary Aneurysms ◽

Intracoronary Thrombolysis ◽

Tissue Plasminogen ◽

X Ray Computed ◽

The Right

An 8-month-old boy presented with right hemiplegia of sudden onset after 20 days of Kawasaki disease, which was not initially treated by gamma globulin. Cranial X-ray computed tomography confirmed cerebral infarction as the cause of the right hemiplegia. In subsequent weeks, he developed multiple thromboses in coronary aneurysms. He successfully underwent intracoronary thrombolysis using tissue plasminogen activator without haemorrhagic complications. Cerebral infarction as a complication of Kawasaki disease is rare, and is a difficult clinical situation to manage.

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