Functional FCGR2B gene variants influence intravenous immunoglobulin response in patients with Kawasaki disease

Shrestha, Sadeep; Wiener, Howard W.; Olson, Aaron K.; Edberg, Jeffrey C.; Bowles, Neil E.; Patel, Hitendra; Portman, Michael A.

doi:10.1016/j.jaci.2011.04.027

Cited by 67 publications

(67 citation statements)

References 12 publications

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“…It is likely that host genetic factors, such as polymorphisms in the Fc gamma receptors, play a role in both the response and resistance to IVIG. 61,202,203 Risk Scores for Predicting Nonresponse to IVIG Approximately 10% to 20% of patients with KD have persistent or recurrent fever after primary therapy with IVIG plus ASA. 204,205 Many studies have shown that patients who are resistant to initial IVIG are at increased risk of developing coronary artery abnormalities.…”

Section: Ivig Resistancementioning

confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

2,863

4,124

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BACKGROUND:Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS:To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and longterm outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS:These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances. K awasaki disease (KD) is an acute, self-limited febrile illness of unknown cause that predominantly affects children <5 years of age. When initially described, the potential for coronary artery complications was not appreciated. KD is now the most common cause of acquired heart disease in children in developed countries. In the absence of pathognomonic tests, the diagnosis continues to rest on the identification of principal clinical findings and the exclusion of other clinically similar entities with known causes. Timely initiation of treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery aneurysms defined from absolute luminal dimensions from 25% to ≈4%. Ongoing studies with additional therapies have not substantially reduced this residual risk. The long-term prognosis is determined by the initial and current level of coronary artery involvement. Certain subsets of patients are at risk for myocardial ischemia from coronary artery thrombosis and stenoses. Medical management of such patients hinges on judicious use of thromboprophylaxis and vigilance to identify evolving stenoses. Invasive revascul...

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Section: Ivig Resistancementioning

confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

2,863

4,124

View full text Add to dashboard Cite

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“…Self-report of population of origin and ethnicity was checked by discriminant analysis of a validated set of 150 ancestry informative markers (AIMs) typed in a previous REACH study (Shrestha et al, 2011). Individuals deemed to be of Hispanic-African American descent (Individuals clustering with the majority of self-reported Hispanic-African American descent) and individuals of admixed population descent other than non-Hispanic African American (individuals with two-component PCA coordinates falling outside the data clusters defining the above ethnic groups and the Caucasian group) were excluded.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial DNA diversity in the African American population

et al. 2013

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Genetic polymorphism along mitochondrial DNA (mtDNA) defines population-specific signatures called mtDNA haplogroups. Estimation of mtDNA haplogroup distribution may be prone to errors, notably if the study sample is not drawn from a multicenter cohort. Here, we report on mtDNA diversity in a sample of African American individuals (n = 343) enrolled in a multicenter cohort. Sequencing of the hypervariable regions I and II of the D-loop control region showed that the most common mitochondrial variants are 73G, 146C, 150T, 152C, 189G, 16278T, and 16311C. In agreement with the published data, we observed 17 common mtDNA haplogroups: L0, L1, L1b, L1c, L2, L2a, L2b, L2c, L2e, L3, L3b, L3d, L3e, L3f, L3h, L3x, and L4. The most commonly observed haplogroup is L2a (19.8%), followed by L1b (10.2%). Overall, the observed mtDNA haplogroup distribution in our study is similar to those published for the African American and the African populations.

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“…Resistance to IVIG could be genotype-dependent or dose-dependent, with an effect after the second IVIG infusion [15,28]. In our study, three patients (6.8%) were IVIG resistant.…”

Section: Treatment Of Patients With Kawasaki Diseasementioning

confidence: 57%

Kawasaki disease – experience of Pediatric University Hospital, Sofia, Bulgaria, 1993–2014. Part II: cardiovascular manifestations and treatment

Telcharova-Mihaylovska

Nikolova

Marinov

et al. 2017

Biotechnology & Biotechnological Equipment

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Kawasaki disease (KD) is a childhood vasculitis syndrome and the coronary arteries are the main target of the vascular damage. The outcome is formation of coronary lesions (CL) that develop in 20%-25% of untreated children. KD is the leading cause of myocardial infarction in infancy. Its consequences among young people are acute coronary syndrome and susceptibility to early atherosclerosis, if the disease were to remain unrecognized. We investigated the cardiac manifestations during the acute phase of the disease, the values of the fever, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the therapeutic factors that created increased coronary risk in our cohort of patients. The study is retrospective . In the cohort (n = 107), 30.8% had coronary lesions, including 19.6% coronary aneurysms and 11.2% significant dilatations. We found association between myocarditis, papillary and left ventricular dysfunction in the acute phase of KD and the risk of coronary aneurysms (p < 0.001). The expressively elevated CRP levels and the persistent fever during the early subacute phase correlated significantly with coronary risk (p < 0.002). The treatment with intravenous immunoglobulin (IVIG) reduced the risk of coronary aneurysms 4.8 times (p < 0.002). A follow-up was performed in 53 children with coronary lesions during the first year of the disease. A longitudinal follow-up was performed in 38 patients. Their results indicate that cardiac monitoring is obligatory for all patients who have experienced KD.

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Functional FCGR2B gene variants influence intravenous immunoglobulin response in patients with Kawasaki disease

Abstract: Capsule Summary In Kawasaki Disease patients, the authors show associations between high-dose intravenous immunoglobulin (IVIG) response and a polymorphism in the FCγRIIB. This provides basis for defining the IVIG regulatory mechanisms and pharmacogenomic approach to IVIG therapy.

Cited by 67 publications

References 12 publications

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Mitochondrial DNA diversity in the African American population

Kawasaki disease – experience of Pediatric University Hospital, Sofia, Bulgaria, 1993–2014. Part II: cardiovascular manifestations and treatment

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