1
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Li P, Chen B, Zhao L, Yang F, Zhang Z, Cao Y, Hu Y. Correlations of FCGR2A 131R/H and FCGR3A 158V/F Polymorphisms with the Susceptibility of Peri-implantitis in Chinese Han Population. Mol Biotechnol 2025; 67:2254-2261. [PMID: 38771420 DOI: 10.1007/s12033-024-01193-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/30/2024] [Indexed: 05/22/2024]
Abstract
The purpose of the study is to investigate the relationship of peri-implantitis (PI) with FCGR2A and FCGR3A gene polymorphisms. One hundred and forty-four patients with PI and 136 patients without PI infection were selected. Gingival crevicular fluid samples were collected from the two groups. The FCGR2A and FCGR3A polymorphism in the two groups were measured. All volunteers were evaluated for periodontal status. The effect of polymorphisms on PI susceptibility was investigated by chi-square analysis and logistic regression. The frequency of FCGR2A rs1801274 GG genotype of PI group was higher than that of the control group, while the GA and AA genotype carriers were less in PI group. After adjusting for other clinical indicators, rs1801274 GA genotype, AA genotype, and the A allele were still negatively correlated with the onset of PI. FCGR3A rs396991 polymorphism was not associated with PI. FCGR2A rs1801274 polymorphism was significantly associated with PI in the Chinese Han population, and GG genotype might be a genetic risk factor for PI.
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Affiliation(s)
- Peng Li
- Department One of Oral and Maxillofacial Surgery, Affiliated Hospital of Tangshan Vocational and Technical College, Tangshan, 063000, China
| | - Bingzhuo Chen
- Fifth Outpatient Department, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210019, China
| | - Liang Zhao
- Department of Stomatology, Central Hospital Affiliated to Shenyang Medical College, No.5, Nanqizi Road, Tiexi District, Shenyang, 110026, China
| | - Feng Yang
- Department of Stomatology, Central Hospital Affiliated to Shenyang Medical College, No.5, Nanqizi Road, Tiexi District, Shenyang, 110026, China
| | - Zhu Zhang
- Department of Stomatology, Central Hospital Affiliated to Shenyang Medical College, No.5, Nanqizi Road, Tiexi District, Shenyang, 110026, China
| | - Yuan Cao
- Department of Stomatology, Central Hospital Affiliated to Shenyang Medical College, No.5, Nanqizi Road, Tiexi District, Shenyang, 110026, China.
| | - Yang Hu
- Department of Oral Restoration and Implantation, First Affiliated Hospital of Xinjiang Medical University/Affiliated Stomatological Hospital, Urumqi, 830054, China.
- Xinjiang Uygur Autonomous Region, Institute of Stomatology, No. 137, Liyushan South Road, Xinshi District, Urumqi, 830054, China.
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2
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Yeşiltepe E, Duman D, Kuyucu N, Bozdoğan ST, Çıtırık L, Yeşil E, Karpuz D. FCGR2A Gene Polymorphism Association in Children with Multisystem Inflammatory Syndrome. Indian Pediatr 2025; 62:372-377. [PMID: 40214943 PMCID: PMC12041097 DOI: 10.1007/s13312-025-00047-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/25/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVE Fc gamma receptor IIa (FCGR2A) gene polymorphism is associated with increased susceptibility to autoimmune and infectious diseases. The aim of the present study was to evaluate the association of FCGR2A rs1801274 polymorphism with the development and severity of multisystem inflammatory syndrome in children (MIS-C). METHODS This case-control study was conducted in a single center with MIS-C patients and healthy children. Clinical and cardiac imaging data of the participants was collected. The association between the clinical severity of the disease and FCGR2A rs1801274 polymorphism were investigated. RESULTS There was no significant association between FCGR2A rs1801274 polymorphism and cardiovascular complications in MIS-C patients. However, those with homozygous FCGR2A rs1801274 gene polymorphism developed severe cardiac dysfunction and required immunomodulatory agents other than intravenous immunoglobulin. The mean age of the patients with severe MIS-C was significantly higher than those with mild MIS-C, and systolic dysfunction was significant. CONCLUSIONS Further multicenter studies in different ethnic groups are needed to evaluate the association between differences in the FCGR2A rs1801274 gene and severity of MIS-C and/or other inflammatory diseases. TRIAL REGISTRY Mersin University Clinical Trial Registry, Decision number 2022/280 dated April 20, 2022.
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Affiliation(s)
- Esra Yeşiltepe
- Department of Pediatrics, Faculty of Medicine, Mersin University, 33343, Mersin, Turkey
| | - Derya Duman
- Department of Pediatric Cardiology, Faculty of Medicine, University of Mersin, 34. Cadde, Ciftlikkoy Kampusu, 33343, Mersin, Turkey.
| | - Necdet Kuyucu
- Department of Pediatric Infectious Disease, Faculty of Medicine, University of Mersin, 34. Cadde, Ciftlikkoy Kampusu, 33343, Mersin, Turkey
| | - Sevcan Tuğ Bozdoğan
- Department of Medical Genetics, Faculty of Medicine, Çukurova University, Balcalı Kampüsü, 01330, Adana, Turkey
| | - Lara Çıtırık
- Department of Pediatric Cardiology, Faculty of Medicine, Mersin University, 33343, Mersin, Turkey
| | - Edanur Yeşil
- Department of Pediatric Infectious Disease, Faculty of Medicine, University of Mersin, 34. Cadde, Ciftlikkoy Kampusu, 33343, Mersin, Turkey
| | - Derya Karpuz
- Department of Pediatric Cardiology, Faculty of Medicine, University of Mersin, 34. Cadde, Ciftlikkoy Kampusu, 33343, Mersin, Turkey
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3
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Kozak K, Pavlyshyn H, Kamyshnyi O, Shevchuk O, Korda M, Vari SG. The Relationship between COVID-19 Severity in Children and Immunoregulatory Gene Polymorphism. Viruses 2023; 15:2093. [PMID: 37896870 PMCID: PMC10612096 DOI: 10.3390/v15102093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/09/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023] Open
Abstract
Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic, but can result in a fatal outcome; therefore, predictions of the disease severity are important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single-nucleotide polymorphisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case-control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS-C) and 15 who were healthy, and who did not have SARS-CoV-2 (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe COVID-19 course and MIS-C in 85.6% of cases. The World Health Organization reported that new SARS-CoV-2 variants may cause previously unseen symptoms in children. Although the study has limitations due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.
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Affiliation(s)
- Kateryna Kozak
- Department of Pediatrics No. 2, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Halyna Pavlyshyn
- Department of Pediatrics No. 2, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Oleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Oksana Shevchuk
- Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Mykhaylo Korda
- Department of Medical Biochemistry, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Sandor G. Vari
- International Research and Innovation in Medicine Program, Cedars–Sinai Medical Center, Los Angeles, CA 90048, USA;
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4
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Liu J, Su D, Yuan P, Ye B, Qin S, Pang Y. Risk Factors for Coronary Artery Aneurysm in a Chinese Pediatric Population with Kawasaki Disease at Low Risk of Intravenous Immunoglobulin Resistance: A Retrospective Cohort Study. Cardiology 2023; 148:457-468. [PMID: 37231847 PMCID: PMC10614276 DOI: 10.1159/000530708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/11/2023] [Indexed: 05/27/2023]
Abstract
INTRODUCTION Multiple scoring systems for predicting intravenous immunoglobulin (IVIG) resistance have been developed. Although low-scoring patients with Kawasaki disease (KD) have a favorable prognosis, many develop coronary artery aneurysms (CAAs). Herein, we determined the risk factors for CAA development among patients with KD with low risk of IVIG resistance. METHODS We compared 14 scoring systems for predicting IVIG resistance among patients with KD hospitalized from 2003 to 2022. Patients were risk stratified using an optimal scoring system. Association between baseline characteristics and CAA development was assessed within the low-risk group. RESULTS Overall, 664 pediatric patients with KD were included; 108 (16.3%) had IVIG resistance, and the Liping scoring system had the highest area under the curve (0.714). According to this system, 444 (66.9%) patients with KD were classified as having low risk of developing IVIG resistance (<5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015-3.730), age <6 months at fever onset (OR, 3.142; 95% CI: 1.028-9.608), and a baseline maximum Z score of ≥2.72 (OR, 3.451; 95% CI: 2.582-4.612). CAA incidence increased with the number of risk factors, and comparisons with a Kobayashi score of <5 points among patients with KD revealed similar results. CONCLUSIONS Predicting the response to IVIG might help further reduce CAA development in patients with KD.
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Affiliation(s)
- Jie Liu
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China,
| | - Danyan Su
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Piaoliu Yuan
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Bingbing Ye
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Suyuan Qin
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Yusheng Pang
- Department of Pediatrics, First Affiliated Hospital, Guangxi Medical University, Nanning, China
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5
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Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease. An Pediatr (Barc) 2022; 97:300-309. [DOI: 10.1016/j.anpede.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 11/16/2021] [Indexed: 11/07/2022] Open
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6
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Beckley MA, Shrestha S, Singh KK, Portman MA. The role of mitochondria in the pathogenesis of Kawasaki disease. Front Immunol 2022; 13:1017401. [PMID: 36300112 PMCID: PMC9592088 DOI: 10.3389/fimmu.2022.1017401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 09/20/2022] [Indexed: 11/28/2022] Open
Abstract
Kawasaki disease is a systemic vasculitis, especially of the coronary arteries, affecting children. Despite extensive research, much is still unknown about the principal driver behind the amplified inflammatory response. We propose mitochondria may play a critical role. Mitochondria serve as a central hub, influencing energy generation, cell proliferation, and bioenergetics. Regulation of these biological processes, however, comes at a price. Release of mitochondrial DNA into the cytoplasm acts as damage-associated molecular patterns, initiating the development of inflammation. As a source of reactive oxygen species, they facilitate activation of the NLRP3 inflammasome. Kawasaki disease involves many of these inflammatory pathways. Progressive mitochondrial dysfunction alters the activity of immune cells and may play a role in the pathogenesis of Kawasaki disease. Because they contain their own genome, mitochondria are susceptible to mutation which can propagate their dysfunction and immunostimulatory potential. Population-specific variants in mitochondrial DNA have also been linked to racial disparities in disease risk and treatment response. Our objective is to critically examine the current literature of mitochondria's role in coordinating proinflammatory signaling pathways, focusing on potential mitochondrial dysfunction in Kawasaki disease. No association between impaired mitochondrial function and Kawasaki disease exists, but we suggest a relationship between the two. We hypothesize a framework of mitochondrial determinants that may contribute to ethnic/racial disparities in the progression of Kawasaki disease.
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Affiliation(s)
- Mikayla A. Beckley
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States
| | - Sadeep Shrestha
- Department of Epidemiology, School of Public Health University of Alabama at Birmingham, Birmingham, AL, United States
| | - Keshav K. Singh
- Department of Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Michael A. Portman
- Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, United States
- Department of Pediatrics, Division of Cardiology, University of Washington, Seattle, WA, United States
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7
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Sánchez-Manubens J, Henares D, Muñoz-Almagro C, Brotons de los Reyes P, Timoneda N, Antón J. Caracterización del microbioma nasofaríngeo en pacientes con enfermedad de Kawasaki. An Pediatr (Barc) 2022. [DOI: 10.1016/j.anpedi.2021.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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8
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Ferdosian F, Dastgheib SA, Hosseini-Jangjou SH, Nafei Z, Lookzadeh MH, Noorishadkam M, Mirjalili SR, Neamatzadeh H. Association of TNF- α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 Polymorphisms with Susceptibility to Kawasaki Disease: A Comprehensive Meta-Analysis. Fetal Pediatr Pathol 2021; 40:320-336. [PMID: 31884867 DOI: 10.1080/15513815.2019.1707917] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Kawasaki Disease (KD) is a multifactorial condition at the junction of infectious diseases, immunology, rheumatology, and cardiology. The aim of this study is to derive a more precise estimation of the association of TNF-α rs1800629, CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms with risk of KD. Methods: PubMed, EMBASE, CNKI databases were searched to identify all relevant studies. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using CMA 2.2 software. Results: A total of 25 studies including eleven studies on TNF-α rs1800629, five studies on CASP3 rs72689236 and nine studies on FCGR2A rs1801274 were selected. Overall, pooled data revealed that CASP3 rs72689236 and FCGR2A rs1801274 polymorphisms were significantly associated with an increased risk of KD. However, there was no significant association between TNF-α rs1800629 and KD. Conclusions: This meta-analysis suggested that CASPS rs72689236 and FCGR2A rs1801274 polymorphisms may modulate individual susceptibility to KD.
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Affiliation(s)
- Farzad Ferdosian
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Seyed Alireza Dastgheib
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Hamed Hosseini-Jangjou
- Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Pediatrics, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Zahra Nafei
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohamad Hosein Lookzadeh
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahmood Noorishadkam
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Seyed Reza Mirjalili
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hossein Neamatzadeh
- Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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9
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Meng L, Zhen Z, Jiang Q, Li XH, Yuan Y, Yao W, Zhang MM, Li AJ, Shi L. Predictive model based on gene and laboratory data for intravenous immunoglobulin resistance in Kawasaki disease in a Chinese population. Pediatr Rheumatol Online J 2021; 19:95. [PMID: 34174887 PMCID: PMC8236184 DOI: 10.1186/s12969-021-00582-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 04/04/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population. METHODS Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019. RESULTS Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset. CONCLUSION Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.
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Affiliation(s)
- Li Meng
- grid.418633.b0000 0004 1771 7032Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China ,grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
| | - Zhen Zhen
- grid.24696.3f0000 0004 0369 153XDepartment of Cardiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Qian Jiang
- grid.418633.b0000 0004 1771 7032Department of Genetics, Capital Institute of Pediatrics, Beijing, China
| | - Xiao-hui Li
- grid.418633.b0000 0004 1771 7032Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China ,grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
| | - Yue Yuan
- grid.24696.3f0000 0004 0369 153XDepartment of Cardiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Wei Yao
- grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
| | - Ming-ming Zhang
- grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
| | - Ai-jie Li
- grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
| | - Lin Shi
- grid.459434.bDepartment of Cardiology, Children’s Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020 China
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10
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Sharma K, Vignesh P, Srivastava P, Sharma J, Chaudhary H, Mondal S, Kaur A, Kaur H, Singh S. Epigenetics in Kawasaki Disease. Front Pediatr 2021; 9:673294. [PMID: 34249810 PMCID: PMC8266996 DOI: 10.3389/fped.2021.673294] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 06/01/2021] [Indexed: 12/17/2022] Open
Abstract
Kawasaki disease (KD) is a common febrile multisystemic inflammatory illness in children that preferentially affects coronary arteries. Children with KD who develop coronary artery aneurysms have a life-long risk of premature coronary artery disease. Hypothesis of inherent predisposition to KD is supported by epidemiological evidence that suggests increased risk of development of disease in certain ethnicities and in children with a previous history of KD in siblings or parents. However, occurrence of cases in clusters, seasonal variation, and very low risk of recurrence suggests an acquired trigger (such as infections) for the development of illness. Epigenetic mechanisms that modulate gene expression can plausibly explain the link between genetic and acquired predisposing factors in KD. Analysis of epigenetic factors can also be used to derive biomarkers for diagnosis and prognostication in KD. Moreover, epigenetic mechanisms can also help in pharmacogenomics with the development of targeted therapies. In this review, we analysed the available literature on epigenetic factors such as methylation, micro-RNAs, and long non-coding RNAs in KD and discuss how these mechanisms can help us better understand the disease pathogenesis and advance the development of new biomarkers in KD.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Surjit Singh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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11
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Kanda S, Fujii Y, Hori SI, Ohmachi T, Yoshimura K, Higasa K, Kaneko K. Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease. CHILDREN-BASEL 2021; 8:children8060433. [PMID: 34064199 PMCID: PMC8224368 DOI: 10.3390/children8060433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/16/2021] [Accepted: 05/19/2021] [Indexed: 11/24/2022]
Abstract
Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10–20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, ORAI1 (rs3741596) and BLK (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.
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Affiliation(s)
- Saki Kanda
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
| | - Yoshimitsu Fujii
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
| | - Shin-ichiro Hori
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
| | - Taichi Ohmachi
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
| | - Ken Yoshimura
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
| | - Koichiro Higasa
- Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan;
| | - Kazunari Kaneko
- Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan; (S.K.); (Y.F.); (S.-i.H.); (T.O.); (K.Y.)
- Correspondence: ; Tel./Fax: +81-72-804-0101
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12
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Hsu YW, Lu HF, Chou WH, Kuo HC, Chang WC. Functional correlations between CXCL10/IP10 gene polymorphisms and risk of Kawasaki disease. Pediatr Allergy Immunol 2021; 32:363-370. [PMID: 32989803 DOI: 10.1111/pai.13381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 09/11/2020] [Accepted: 09/12/2020] [Indexed: 12/01/2022]
Abstract
BACKGROUND Kawasaki disease (KD) is an acute systemic vasculitis syndrome with unknown pathogen. The immune system has been suggested to involve in the pathogenesis in KD. IP10 is a chemoattractant for initiating T-cell activation. The aim of this study was to investigate the association between genetic polymorphisms of IP10 and KD. METHODS A total of 354 KD patients and 1,709 control subjects (709 subjects in cohort 1 and 1,000 subjects in cohort 2) were enrolled in this study. Four tagging single nucleotide polymorphisms (rs3921, rs4256246, rs4508917, and rs4386624) were chosen for genotyping. RESULTS Our results indicated that CC genotype of rs3921 and GG genotype of rs4386624 had higher frequency in KD patients compared to control. In addition, higher plasma IP10 level was observed in CC genotype of rs3921 than CG genotype and GG genotype. C/G haplotype carriers of rs3921/rs4386624 had 5.48-fold risk for KD compared to G/C haplotype carriers. Two-locus analysis further showed the combinatorial effects of rs3921 and rs4386624 in KD susceptibility. CONCLUSIONS This study indicated the close correlation between IP10 and the risk of Kawasaki disease.
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Affiliation(s)
- Yu-Wen Hsu
- The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.,Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Hsing-Fang Lu
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
| | - Wan-Hsuan Chou
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Ho-Chang Kuo
- Master's Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Wei-Chiao Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,Master's Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
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13
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Abstract
Kawasaki disease (KD) is a medium vessel vasculitis that affects young children. Despite extensive research over the last 50 years, the etiology of KD remains an enigma. Seasonal change in wind patterns was shown to have correlation with the epidemics of KD in Japan. Occurrence of disease in epidemiological clusters, seasonal variation, and a very low risk of recurrence suggest that KD is triggered by an infectious agent. The identification of oligoclonal IgA response in the affected tissues suggests an antigen-driven inflammation. The recent identification of a viral antigen in the cytoplasm of bronchial ciliated epithelium also favors infection as the main trigger for KD. Pointers that suggest a genetic basis of KD include a high disease prevalence in North-East Asian populations, a high risk among siblings, and familial occurrence of cases. Dysregulated innate and adaptive immune responses are evident in the acute stages of KD. In addition to the coronary wall inflammation, endothelial dysfunction and impaired vascular remodeling contribute to the development of coronary artery abnormalities (CAAs) and thrombosis. Genetic aberrations in certain intracellular signaling pathways involving immune effector functions are found to be associated with increased susceptibility to KD and development of coronary artery abnormalities (CAAs). Several susceptible genes have been identified through genome-wide association studies (GWAS) and linkage studies (GWLS). The genes that are studied in KD can be classified under 4 major groups-enhanced T cell activation (ITPKC, ORAI1, STIM1), dysregulated B cell signaling (CD40, BLK, FCGR2A), decreased apoptosis (CASP3), and altered transforming growth factor beta signaling (TGFB2, TGFBR2, MMP, SMAD). The review aims to highlight the role of several genetic risk factors that are linked with the increased susceptibility to KD.
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Affiliation(s)
- Rajni Kumrah
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Pandiarajan Vignesh
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
| | - Amit Rawat
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Surjit Singh
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
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14
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Beghi S, Cavaliere F, Buschini A. Gene polymorphisms in calcium-calmodulin pathway: Focus on cardiovascular disease. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2020; 786:108325. [PMID: 33339582 DOI: 10.1016/j.mrrev.2020.108325] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 07/22/2020] [Accepted: 07/24/2020] [Indexed: 12/30/2022]
Abstract
Cardiovascular disease is the leading cause of death in industrialized countries and affects an increasing number of people. Several risk factors play an important role in the etiology of this disease, such as an unhealthy lifestyle. It is increasingly clear that genetic factors influencing the molecular basis of excitation-contraction mechanisms in the heart could contribute to modify the individual's risk. Thanks to the progress that has been made in understanding calcium signaling in the heart, it is assumed that calmodulin can play a crucial role in the excitation-contraction coupling. In fact, calmodulin (CaM) binds calcium and consequently regulates calcium channels. Several works show how some polymorphic variants can be considered predisposing factors to complex pathologies. Therefore, we hypothesize that the identification of polymorphic variants of proteins involved in the CaM pathway could be important for understanding how genetic traits can influence predisposition to myocardial infarction. This review considers each pathway of the three different isoforms of calmodulin (CaM1; CaM2; CaM3) and focuses on some common proteins involved in the three pathways, with the aim of analyzing the polymorphisms studied in the literature and understanding if they are associated with cardiovascular disease.
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Affiliation(s)
- Sofia Beghi
- University of Parma, Department of Chemistry, Life Sciences and Environmental Sustainability, Parco Area Delle Scienze 11A, 43124, Parma, Italy
| | - Francesca Cavaliere
- University of Parma, Department of Food and Drug, Parco Area Delle Scienze 17A, 43124, Parma, Italy
| | - Annamaria Buschini
- University of Parma, Department of Chemistry, Life Sciences and Environmental Sustainability, Parco Area Delle Scienze 11A, 43124, Parma, Italy.
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15
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Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample. Sci Rep 2020; 10:11756. [PMID: 32678208 PMCID: PMC7366615 DOI: 10.1038/s41598-020-68673-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 06/25/2020] [Indexed: 12/17/2022] Open
Abstract
Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10–5; C allele, OR = 1.32, P = 8.1 × 10–4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.
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16
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Hicar MD. Antibodies and Immunity During Kawasaki Disease. Front Cardiovasc Med 2020; 7:94. [PMID: 32671098 PMCID: PMC7326051 DOI: 10.3389/fcvm.2020.00094] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 04/30/2020] [Indexed: 12/14/2022] Open
Abstract
The cause of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology studies support that an infectious disease is involved in at least starting the inflammatory cascade set off during KD. Clues from epidemiology support that humoral immunity can have a protective effect. However, the role of the immune system, particularly of B cells and antibodies, in pathogenesis of KD is still unclear. Intravenous immunoglobulin (IVIG) and other therapies targeted at modulating inflammation can prevent development of coronary aneurysms. A number of autoantibody responses have been reported in children with KD and antibodies have been generated from aneurysmal plasma cell infiltrates. Recent reports show that children with KD have similar plasmablast responses as other children with infectious diseases, further supporting an infectious starting point. As ongoing studies are attempting to identify the etiology of KD through study of antibody responses, we sought to review the role of humoral immunity in KD pathogenesis, treatment, and recovery.
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Affiliation(s)
- Mark Daniel Hicar
- University at Buffalo, Buffalo, NY, United States.,John R. Oishei Children's Hospital, Buffalo, NY, United States.,Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
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17
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Wang Z, Geng PL. CD32a polymorphism rs1801274 affects the risk of Kawasaki disease. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2020; 48:620-626. [PMID: 32072832 DOI: 10.1080/21691401.2019.1645156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Aim: To analyze the impact of CD32a polymorphism rs1801274 on the occurrence of Kawasaki disease (KD) through the meta-analysis.Methods: The correlation between CD32a polymorphism rs1801274 and the susceptibility to KD was appraised using summarized odds ratios (ORs) with their 95% confidence intervals (95% CIs). Besides, stratification analyses were further implemented on the basis of ethnicity and control source, respectively. Between-study heterogeneity was checked adopting chi-square-based Q test, with p < .05 as significant level. And results from Q test determined which model would be employed for OR calculation, fixed- or random-effects. Sensitivity analysis was accomplished to test the stability of final results. Potential publication bias among included studies was investigated using Begg's funnel plot and Egger's test. If publication bias was significant, its influence on overall estimates would be measured adopting the trim-and-fill method.Results: CD32a polymorphism rs1801274 significantly increased KD risk in total analysis under the comparisons of AA vs. GG, AA + AG vs. GG, AA vs. GG + AG, A vs. G and AG vs. GG (OR = 2.69, 95% CI = 1.39-5.20; OR = 2.00, 95% CI = 1.23-3.26; OR = 1.90, 95% CI = 1.23-2.94; OR = 1.77, 95% CI = 1.34-2.34; OR = 1.53, 95% CI = 1.07-2.19). After stratification analysis by ethnicity, similar tendency was also observed in Caucasian and Asian subgroups under corresponding genetic models. And parallel results were replicated in population-based and other-source subgroups after stratified analysis by control source, under some contrasts.Conclusion: CD32a polymorphism rs1801274 has strong relation to KD onset, and the presence of its A allele could elevate the disease incidence.
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Affiliation(s)
- Zhiyong Wang
- Department of Pediatrics, Weifang Maternal and Child Health Hospital, Weifang, China
| | - Pei-Liang Geng
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
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18
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Shimomura M, Okura Y, Ohta O, Takahashi Y, Kobayashi I. Autoimmune haemolytic anaemia caused by anti-M antibody in a patient with Kawasaki disease. Mod Rheumatol Case Rep 2020; 4:99-101. [PMID: 33086950 DOI: 10.1080/24725625.2019.1681654] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Intravenous immunoglobulin (IVIG) is a standard therapy for Kawasaki disease (KD), because it prevents formation of coronary artery aneurysm, a major complication of KD. Herein, we report a 3-year-old boy with KD complicated by haemolytic anaemia (HA) which developed following two courses of IVIG. Although both direct and indirect antiglobulin tests and anti-M antibodies were positive in his blood obtained after the onset of HA, indirect antiglobulin tests and anti-M antibodies were negative either in the blood sample before the treatment or the same lot of IVIG products as those used for the therapy, suggesting autoimmune mechanism. This is, to our knowledge, the first report of autoimmune HA caused by anti-M autoantibodies after IVIG therapy in KD.
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Affiliation(s)
- Masaki Shimomura
- Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center, Sapporo, Japan
| | - Yuka Okura
- Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center, Sapporo, Japan
| | - Osamu Ohta
- Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center, Sapporo, Japan
| | - Yutaka Takahashi
- Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center, Sapporo, Japan
| | - Ichiro Kobayashi
- Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center, Sapporo, Japan
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19
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van Stijn D, Slegers A, Zaaijer H, Kuijpers T. Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System. Front Pediatr 2020; 8:627957. [PMID: 33585370 PMCID: PMC7873854 DOI: 10.3389/fped.2020.627957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 12/21/2020] [Indexed: 12/03/2022] Open
Abstract
Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls. Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group. Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.
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Affiliation(s)
- Diana van Stijn
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Annemarie Slegers
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Hans Zaaijer
- Laboratory of Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Taco Kuijpers
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
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20
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Chaudhary H, Nameirakpam J, Kumrah R, Pandiarajan V, Suri D, Rawat A, Singh S. Biomarkers for Kawasaki Disease: Clinical Utility and the Challenges Ahead. Front Pediatr 2019; 7:242. [PMID: 31275907 PMCID: PMC6591436 DOI: 10.3389/fped.2019.00242] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/28/2019] [Indexed: 12/11/2022] Open
Abstract
Kawasaki disease (KD) has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the developed world and is increasingly being recognized from several developing countries. It is a systemic vasculitis with a predilection for coronary arteries. The diagnosis is based on a constellation of clinical findings that appear in a temporal sequence. Quite understandably, this can become a problem in situations wherein the clinical features are not typical. In such situations, it can be very difficult, if not impossible, to arrive at a diagnosis. Several biomarkers have been recognized in children with acute KD but none of these has reasonably high sensitivity and specificity in predicting the course of the illness. A line up of inflammatory, proteomic, gene expression and micro-RNA based biomarkers has been studied in association with KD. The commonly used inflammatory markers e.g. erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and total leucocyte counts (TLC) lack specificity for KD. Proteomic studies are based on the identification of specific proteins in serum, plasma and urine by gel electrophoresis. A host of genetic studies have identified genes associated with KD and some of these genes can predict the course and coronary outcomes in the affected individuals. Most of these tests are in the early stages of their development and some of these can predict the course, propensity to develop coronary artery sequelae, intravenous immunoglobulin (IVIg) resistance and the severity of the illness in a patient. Development of clinical criteria based on these tests will improve our diagnostic acumen and aid in early identification and prevention of cardiovascular complications.
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Affiliation(s)
| | | | | | | | | | | | - Surjit Singh
- Post Graduate Institute of Medical Education and Research, Chandigarh, India
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21
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Menikou S, Langford PR, Levin M. Kawasaki Disease: The Role of Immune Complexes Revisited. Front Immunol 2019; 10:1156. [PMID: 31263461 PMCID: PMC6584825 DOI: 10.3389/fimmu.2019.01156] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 05/07/2019] [Indexed: 01/09/2023] Open
Abstract
Kawasaki disease (KD) is an inflammatory disease in children associated with vasculitis affecting predominantly the coronary arteries and is now the most common cause of acquired heart disease in children in developed countries. The etiology of KD is unknown but epidemiological studies implicate an infectious agent or toxin, which causes disease in genetically predisposed individuals. The presence of immune complexes (ICs) in the serum of children with KD was established in numerous studies during the 1970s and 80s. More recent genetic studies have identified variation in Fcγ receptors and genes controlling immunoglobulin production associated with KD. In this review we link the genetic findings and IC studies and suggest a key role for their interaction in pathophysiology of the disease.
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Affiliation(s)
- Stephanie Menikou
- Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom
| | - Paul R Langford
- Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom
| | - Michael Levin
- Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom
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22
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Nagelkerke SQ, Tacke CE, Breunis WB, Tanck MWT, Geissler J, Png E, Hoang LT, van der Heijden J, Naim ANM, Yeung RSM, Levin ML, Wright VJ, Burgner DP, Ponsonby AL, Ellis JA, Cimaz R, Shimizu C, Burns JC, Fijnvandraat K, van der Schoot CE, van den Berg TK, de Boer M, Davila S, Hibberd ML, Kuijpers TW. Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease. Front Immunol 2019; 10:185. [PMID: 30949161 PMCID: PMC6437109 DOI: 10.3389/fimmu.2019.00185] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 01/21/2019] [Indexed: 12/23/2022] Open
Abstract
The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r2 = 0.63). LD between these two variants was weaker (r2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency <0.005%). The FCGR2C-ORF haplotype and rs1801274 (FCGR2A-H131R) were in weak LD (r2 = 0.08) in Europeans. We evaluated the importance of ethnic variation and LD in Kawasaki Disease (KD), an acute vasculitis in children with increased incidence in Asians. An association of rs1801274 with KD was previously shown in ethnically diverse genome-wide association studies. Now, we show in 1,028 European KD patients that the FCGR2C-ORF haplotype, although nearly absent in Asians, was more strongly associated with susceptibility to KD than rs1801274 in Europeans. Our data illustrate the importance of interpreting findings of association studies concerning the FCGR2/3 locus with knowledge of LD and ethnic variation.
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Affiliation(s)
- Sietse Q Nagelkerke
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Carline E Tacke
- Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Willemijn B Breunis
- Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Michael W T Tanck
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Judy Geissler
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Eileen Png
- Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore
| | - Long T Hoang
- Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore
| | - Joris van der Heijden
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Ahmad N M Naim
- Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore
| | - Rae S M Yeung
- Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Michael L Levin
- Department of Pediatrics, Imperial College London, London, United Kingdom
| | - Victoria J Wright
- Department of Pediatrics, Imperial College London, London, United Kingdom
| | - David P Burgner
- Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
| | - Anne-Louise Ponsonby
- Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
| | - Justine A Ellis
- Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.,Faculty of Health, Centre for Social and Early Emotional Development, Deakin University, Burwood, VIC, Australia
| | - Rolando Cimaz
- Rheumatology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Chisato Shimizu
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, United States
| | - Jane C Burns
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, United States
| | - Karin Fijnvandraat
- Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Department of Plasma Proteins, Sanquin Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - C Ellen van der Schoot
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Timo K van den Berg
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Martin de Boer
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Sonia Davila
- Human Genetics, Genome Institute of Singapore, Singapore, Singapore
| | - Martin L Hibberd
- Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore.,Department of Pathogen Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Taco W Kuijpers
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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23
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Pi L, Xu Y, Fu L, Zhang L, Liu Y, Zhou H, Che D, Gu X. A PEAR1 polymorphism (rs12041331) is associated with risk of coronary artery aneurysm in Kawasaki disease. Ann Hum Genet 2018; 83:54-62. [PMID: 30256383 DOI: 10.1111/ahg.12285] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 07/24/2018] [Accepted: 07/25/2018] [Indexed: 12/18/2022]
Abstract
Kawasaki disease (KD) is an acute systemic vasculitis that is most seriously complicated by coronary artery aneurysm (CAA). The polymorphisms of platelet endothelial aggregation receptor 1 (PEAR1), notably rs12041331 and rs12566888, were found to be closely related to cardiac disease. However, little is known regarding the connection between PEAR1 and KD. In this study, we genotyped PEAR1 rs12566888 and rs12041331 in 637 healthy infants and 694 KD patients (74 with CAA). Subsequently, odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the strength of their relationships. No significant differences in the frequency of rs12566888 or rs12041331 in PEAR1 were observed between KD and healthy controls. However, regardless of the statistical combination of rs12566888 genotype, the rs12041331 recessive inheritance model was associated with an increased risk of CAA after Bonferroni correction (for rs12041331, AA vs. GG/GA: adjusted OR = 2.37, 95% CI = 1.41-4.01, P = 0.009; combination of two recessive genotypes vs. combination of 0-1 recessive genotypes: adjusted OR = 2.39, 95% CI = 1.42-4.04, P = 0.009). This study suggests for the first time that PEAR1 polymorphisms did not indicate susceptibility for KD occurrence but the rs12041331 polymorphism was associated with increased risk of CAA formation in KD, and the functions of the gene warrant further research.
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Affiliation(s)
- Lei Pi
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yufen Xu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Lanyan Fu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Li Zhang
- Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yunfeng Liu
- Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Huazhong Zhou
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Di Che
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Xiaoqiong Gu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.,Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
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Che D, Li J, Fu L, Pi L, Rong X, Wang Y, Xu Y, Huang P, Chu M, Gu X. The rs1625579 T>G polymorphism in the miRNA-13 gene confers a risk of early- onset Kawasaki disease in a southern Chinese population. Infect Drug Resist 2018; 11:1055-1060. [PMID: 30122962 PMCID: PMC6082322 DOI: 10.2147/idr.s174140] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Kawasaki disease (KD) mainly manifests as excessive inflammation and vascular endothelial cell injury. This disease generally occurs in children younger than 5 years of age and is more severe in children younger than 12 months. KD affects males and females at a ratio of 1.5:1. Polymorphisms of the rs1625579 locus in the miR-13 gene are associated with schizophrenia susceptibility, and high glucose-induced upregulation of miR-137 in vascular endothelial cells promotes monocyte chemotaxis and inflammatory cytokine secretion in gestational diabetes mellitus. However, researchers have not reported whether rs1625579 is associated with KD susceptibility or onset. Therefore, we investigated the relationship between the miRNA-13 rs1625579 T>G polymorphism and KD susceptibility. METHODS TaqMan real-time polymerase chain reaction was applied to determine the genotypes of 532 patients with KD (365 males and 167 females) and 623 control subjects (402 males and 221 females). RESULTS Comparison of all cases with all controls revealed that the rs1625579 T>G polymorphism was not associated with KD susceptibility. However, a subgroup analysis revealed that subjects with the rs1625579 TG/GG genotypes exhibited a significantly higher onset risk for KD before 12 months of age than carriers of the TT genotype (adjusted age and gender odds ratio=1.99, 95% CI=1.04-3.83; P=0.039). CONCLUSION Our results indicate that the rs1625579 T>G polymorphism confers a risk of early-onset KD in southern Chinese children.
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Affiliation(s)
- Di Che
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
| | - Jiawen Li
- Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou, China,
| | - Lanyan Fu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
| | - Lei Pi
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
| | - Xing Rong
- Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou, China,
| | - Yanfei Wang
- Department of Cardiology, Guangzhou Women and Children's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yufen Xu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
| | - Ping Huang
- Department of Cardiology, Guangzhou Women and Children's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Maoping Chu
- Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou, China,
| | - Xiaoqiong Gu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
- Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China,
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Kuo HC, Wong HSC, Chang WP, Chen BK, Wu MS, Yang KD, Hsieh KS, Hsu YW, Liu SF, Liu X, Chang WC. Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease. ACTA ACUST UNITED AC 2018; 10:CIRCGENETICS.116.001625. [PMID: 29025760 PMCID: PMC5647111 DOI: 10.1161/circgenetics.116.001625] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 07/27/2017] [Indexed: 12/30/2022]
Abstract
Supplemental Digital Content is available in the text. Background— Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. Methods and Results— To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher’s exact P value 4.518×10−03 and 8.224×10−10, respectively). Conclusions— This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.
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Affiliation(s)
- Ho-Chang Kuo
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Henry Sung-Ching Wong
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Wei-Pin Chang
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Ben-Kuen Chen
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Mei-Shin Wu
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Kuender D Yang
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Kai-Sheng Hsieh
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Yu-Wen Hsu
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Shih-Feng Liu
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Xiao Liu
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.)
| | - Wei-Chiao Chang
- From the Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy (H.-C.K., W.-C.C.), Department of Clinical Pharmacy, School of Pharmacy (H.S.-C.W., M.-S.W., W.-C.C.), School of Health Care Administration, College of Management (W.-P.C.), and PhD Program in Biotechnology Research and Development, College of Pharmacy (W.-C.C.), Taipei Medical University, Taiwan; Department of Pediatrics and Kawasaki Disease Center (H.-C.K., K.-S.H.), Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine (S.-F.L.), and Department of Respiratory Therapy (S.-F.L.), Kaohsiung Chang Gung Memorial Hospital, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan (B.-K.C.); Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan (K.D.Y.); Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan (K.D.Y.); The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taiwan (Y.-W.H.); Section of Hematology/Oncology, Department of Medicine, The University of Chicago, IL (X.L.); Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taiwan (W.-C.C.); and Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan (W.-C.C.).
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The CD40 rs1883832 Polymorphism Affects Sepsis Susceptibility and sCD40L Levels. BIOMED RESEARCH INTERNATIONAL 2018; 2018:7497314. [PMID: 29780830 PMCID: PMC5892284 DOI: 10.1155/2018/7497314] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 01/09/2018] [Accepted: 02/14/2018] [Indexed: 01/09/2023]
Abstract
Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.
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Zhang C, Wang W, Zhang H, Wei L, Guo S. Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis. Oncotarget 2018; 7:39436-39443. [PMID: 27270653 PMCID: PMC5129943 DOI: 10.18632/oncotarget.9831] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 05/28/2016] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. METHODS A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. RESULTS A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. CONCLUSIONS This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations.
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Affiliation(s)
- Chang'e Zhang
- Department of Dermatology, Zhengzhou Children's Hospital, Henan, China
| | - Wenju Wang
- Department of Dermatology, The Second People's Hospital in Chengdu, Sichuan, China
| | - Hong'e Zhang
- Department of Medicine, Xiangfu District Hospital of Traditional Chinese Medicine, Kaifeng, Henan, China
| | - Lulu Wei
- Department of Dermatology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Shuping Guo
- Department of Dermatology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
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Dissecting Kawasaki disease: a state-of-the-art review. Eur J Pediatr 2017; 176:995-1009. [PMID: 28656474 PMCID: PMC5511310 DOI: 10.1007/s00431-017-2937-5] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 05/11/2017] [Accepted: 05/15/2017] [Indexed: 12/12/2022]
Abstract
UNLABELLED Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities. Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children. Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA. Unfortunately, 10-20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment. Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases. Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA. Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur. These complications are most likely to arise in the largest, so-called giant CAA. Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself. CONCLUSION Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA. Since children with previous KD are entering adulthood, long-term follow-up is increasingly important. What is known: • Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication. • Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood. What is new: • In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway. • As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.
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Kuo HC, Li SC, Guo MMH, Huang YH, Yu HR, Huang FC, Jiao F, Kuo HC, Andrade J, Chan WC. Genome-Wide Association Study Identifies Novel Susceptibility Genes Associated with Coronary Artery Aneurysm Formation in Kawasaki Disease. PLoS One 2016; 11:e0154943. [PMID: 27171184 PMCID: PMC4865092 DOI: 10.1371/journal.pone.0154943] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 04/21/2016] [Indexed: 11/18/2022] Open
Abstract
Kawasaki disease (KD) or Kawasaki syndrome is known as a vasculitis of small to medium-sized vessels, and coronary arteries are predominantly involved in childhood. Generally, 20-25% of untreated with IVIG and 3-5% of treated KD patients have been developed coronary artery lesions (CALs), such as dilatation and aneurysm. Understanding how coronary artery aneurysms (CAAs) are established and maintained in KD patients is therefore of great importance. Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10(-9); OR = 32.22) and rs7922552 (P = 8.43 × 10(-9); OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10(-9); OR = 21.03)). Their known functions have been reported to associate with cardiac muscle and tubulin, respectively. As a result, this might imply their putative roles of establishing CAAs during KD progression. Additionally, various model analyses have been utilized to determine dominant and recessive inheritance patterns of identified susceptibility mutations. Finally, all susceptibility genes hit by significant genetic variants were further investigated and the top three representative gene-ontology (GO) clusters were regulation of cell projection organization, neuron recognition, and peptidyl-threonine phosphorylation. Our results help to depict the potential routes of the pathogenesis of CAAs in KD patients and will facilitate researchers to improve the diagnosis and prognosis of KD in personalized medicine.
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Affiliation(s)
- Ho-Chang Kuo
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sung-Chou Li
- Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mindy Ming-Huey Guo
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ying-Hsien Huang
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hong-Ren Yu
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fu-Chen Huang
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fuyong Jiao
- Children's Hospital of Shaanxi Provincial People's Hospital and Jiaotong University, Xi'an, China
| | - Hsing-Chun Kuo
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Jorge Andrade
- Center for Research Informatics, The University of Chicago, Chicago, Illinois, 60637, United States of America
| | - Wen-Ching Chan
- Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Center for Research Informatics, The University of Chicago, Chicago, Illinois, 60637, United States of America
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Yu JJ. Use of corticosteroids during acute phase of Kawasaki disease. World J Clin Pediatr 2015; 4:135-142. [PMID: 26566486 PMCID: PMC4637804 DOI: 10.5409/wjcp.v4.i4.135] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 08/28/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.
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