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Zhang Z, Wang C, Liu Q, Xiao Y, Zhou J, Wu K, Huang Y, Zhang Z, Liu S, Lin Q. The risk of malnutrition as a predictor of arrhythmia recurrence after catheter ablation in patients with paroxysmal non-valvular atrial Fibrillation and heart failure with preserved ejection fraction. PLoS One 2025; 20:e0317721. [PMID: 39888955 PMCID: PMC11785320 DOI: 10.1371/journal.pone.0317721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 01/05/2025] [Indexed: 02/02/2025] Open
Abstract
BACKGROUND Malnutrition presents a significant challenge in managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF), yet its impact on AF recurrence after catheter ablation in this population remains unclear. METHODS We conducted a retrospective analysis of 204 patients with paroxysmal non-valvular AF and HFpEF who underwent radiofrequency or cryoballoon ablation. Risk of malnutrition as assessed using three screening tools: the Controlling Nutritional Status (CONUT) score, Prognostic Nutritional Index (PNI), and Nutritional Risk Index (NRI)]. We examined the relationship between risk of malnutrition and AF recurrence post-ablation. RESULTS After a mean follow-up period of 11.2 ± 1.8 months, 43 patients (21.1%) experienced AF recurrence. Despite being classified as overweight or obese based on body mass index, many patients were at risk of malnutrition according to the CONUT score, NRI, and PNI. Adjusted analyses showed that higher CONUT scores (HR: 10.132; 95% CI: 2.545-40.336; P = 0.001), lower NRI (HR: 22.734; 95% CI: 6.399-80.776; P < 0.001), or lower PNI (HR: 9.469; 95% CI: 3.232-27.739; P < 0.001) were significantly associated with increased risk of AF recurrence. Restricted cubic spline regression revealed an inverted U-shaped relationship between the CONUT score and AF recurrence, and L-shaped relationships for both NRI and PNI with AF recurrence. CONCLUSIONS Systematic nutritional assessment is crucial in patients with paroxysmal non-valvular AF and HFpEF. High CONUT scores, low NRI, or low PNI serve as independent predictors for AF recurrence. Further large-scale randomized controlled trials are required to validate these findings.
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Affiliation(s)
- Zixi Zhang
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Cancan Wang
- Department of Endocrinology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Qiming Liu
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Yichao Xiao
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Jiabao Zhou
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Keke Wu
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Yunying Huang
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Zeying Zhang
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Shiping Liu
- Department of Nutritional Sciences, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
| | - Qiuzhen Lin
- Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China
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Kumrah R, Goyal T, Rawat A, Singh S. Markers of Endothelial Dysfunction in Kawasaki Disease: An Update. Clin Rev Allergy Immunol 2024; 66:99-111. [PMID: 38462555 DOI: 10.1007/s12016-024-08985-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 03/12/2024]
Abstract
Kawasaki disease (KD) is a medium vessel vasculitis that has a special predilection for coronary arteries. Cardiovascular complications include the development of coronary artery abnormalities (CAAs) and myocarditis. Endothelial dysfunction (ED) is now recognized to be a key component in the pathogenesis of KD and is believed to contribute to the development of CAAs. ED has been evaluated by several clinical parameters. However, there is paucity of literature on laboratory markers for ED in KD. The evaluation of ED can be aided by the identification of biomarkers such as oxidative stress markers, circulating cells and their progenitors, angiogenesis factors, cytokines, chemokines, cell-adhesion molecules, and adipokines. If validated in multicentric studies, these biomarkers may be useful for monitoring the disease course of KD. They may also provide a useful predictive marker for the development of premature atherosclerosis that is often a concern during long-term follow-up of KD. This review provides insights into the current understanding of the significance of ED in KD.
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Affiliation(s)
- Rajni Kumrah
- Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Taru Goyal
- Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Amit Rawat
- Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Surjit Singh
- Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Sunaga Y, Watanabe A, Katsumata N, Toda T, Yoshizawa M, Kono Y, Hasebe Y, Koizumi K, Hoshiai M, Kawakami E, Inukai T. A simple scoring model based on machine learning predicts intravenous immunoglobulin resistance in Kawasaki disease. Clin Rheumatol 2023; 42:1351-1361. [PMID: 36627530 PMCID: PMC9832252 DOI: 10.1007/s10067-023-06502-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/25/2022] [Accepted: 12/30/2022] [Indexed: 01/12/2023]
Abstract
INTRODUCTION In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions. OBJECTIVE To establish a simple scoring model predicting IVIG resistance in KD patients based on the machine learning model. METHODS A retrospective cohort study of 1002 KD patients diagnosed at 12 facilities for 10 years, in which 22.7% were resistant to initial IVIG treatment. We performed machine learning with diverse models using 30 clinical variables at diagnosis in 801 and 201 cases for training and test datasets, respectively. SHAP was applied to identify the variables that influenced the prediction model. A scoring model was designed using the influential clinical variables based on the Shapley additive explanation results. RESULTS Light gradient boosting machine model accurately predicted IVIG resistance (area under the receiver operating characteristic curve (AUC), 0.78; sensitivity, 0.50; specificity, 0.88). Next, using top three influential features (days of illness at initial therapy, serum levels of C-reactive protein, and total cholesterol), we designed a simple scoring system. In spite of its simplicity, it predicted IVIG resistance (AUC, 0.72; sensitivity, 0.49; specificity, 0.82) as accurately as machine learning models. Moreover, accuracy of our scoring system with three clinical features was almost identical to that of Gunma score with seven clinical features (AUC, 0.73; sensitivity, 0.53; specificity, 0.83), a well-known logistic regression scoring model. CONCLUSION A simple scoring system based on the findings in machine learning seems to be a useful tool to accurately predict IVIG resistance in KD patients.
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Affiliation(s)
- Yuto Sunaga
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Atsushi Watanabe
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Nobuyuki Katsumata
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
- Department of Neonatology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan
| | - Takako Toda
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
| | - Masashi Yoshizawa
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Yosuke Kono
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Yohei Hasebe
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Keiichi Koizumi
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
- Department of Pediatrics, Fujiyoshida Municipal Hospital, Fujiyoshida, Yamanashi, Japan
| | - Minako Hoshiai
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
- Department of Pediatrics, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan
| | - Eiryo Kawakami
- Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
- Institute for Advanced Academic Research (IAAR), Chiba University, Chiba, Japan
- Advanced Data Science Project, RIKEN Information R&D and Strategy Headquarters, Kanagawa, Japan
| | - Takeshi Inukai
- Faculty of Medicine, Department of Pediatrics, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
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Mandal SK, Tare M, Deepa PR. COVID-19 infection and metabolic comorbidities: Mitigating role of nutritional sufficiency and drug - nutraceutical combinations of vitamin D. HUMAN NUTRITION & METABOLISM 2023; 31:200179. [PMID: 38620788 PMCID: PMC9762046 DOI: 10.1016/j.hnm.2022.200179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
The vulnerability of human health is amplified in recent times with global increase in non-communicable diseases (due to lifestyle changes and environmental insults) and infectious diseases (caused by newer pathogens and drug-resistance strains). Clinical management of diseases is further complicated by disease severity caused by other comorbid factors. Drug-based therapy may not be the sole approach, particularly in scenarios like the COVID-19 pandemic, where there is no specific drug against SARS-CoV-2. Nutritional interventions are significant in armouring human populations in disease prevention, and as adjunctive therapy for disease alleviation. Amidst ongoing clinical trials to determine the efficacy of Vit. D against infections and associated complications, this review examines the pleiotropic benefits of nutritional adequacy of vitamin D (Vit. D) in combating viral infections (COVID-19), its severity and complications due to co-morbidities (obesity, diabetes, stroke and Kawasaki disease), based on research findings and clinical studies. Supplements of Vit. D in combination with other nutrients, and drugs, are suggested as promising preventive-health and adjunct-treatment strategies in the clinical management of viral infections with metabolic comorbidities.
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Affiliation(s)
- Sumit Kumar Mandal
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
| | - Meghana Tare
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
| | - P R Deepa
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, India
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Praharaj DL, Rawat A, Gupta A, Arora K, Pilania RK, Bhattad S, Singh S. Adipocytokine profile in children with Kawasaki disease at a mean follow-up period of 5.5 years: A study from North India. World J Clin Pediatr 2022; 11:360-368. [PMID: 36052116 PMCID: PMC9331403 DOI: 10.5409/wjcp.v11.i4.360] [Citation(s) in RCA: 3] [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: 03/31/2021] [Revised: 08/21/2021] [Accepted: 05/12/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Kawasaki disease (KD) is an acute self-limited vasculitis with a predilection for coronary arteries. Children with KD may have altered lipid metabolism and abnormal lipid profiles that may last for prolonged periods. However, there is a paucity of literature on the role of adipocytokines in KD. AIM To estimate the levels of adipocytokines (adiponectin, leptin and resistin) during the convalescent phase of KD. METHODS Twenty children, who had KD at least three years earlier, were enrolled in this study. In addition, 20 healthy controls were also enrolled. Clinical and laboratory profiles of patients were obtained from hospital records. Serum adiponectin, leptin and resistin levels were estimated by enzyme-linked immunosorbent assay. RESULTS Mean age of the patients in the study group was 10.15 ± 3 years and the male: female ratio was 1.5:1. Median serum resistin levels in patients with KD (27.77 ng/mL; [IQR: 18.66, 48.90]) were decreased compared to controls (21.20 ng/mL; [IQR: 14.80, 27.00]) (P = 0.04). Median serum leptin levels in cases and controls were 1.83 ng/mL; (IQR: 1.13, 3.80), and 1.10 ng/mL; (IQR: 0.41, 2.88), respectively (P = 0.09). Median serum adiponectin levels were similar in both cases (12.20 µg/mL; [IQR: 9.76, 17.97]) and controls (13.95 µg/mL; [IQR: 11.17, 22.58]); (P = 0.18). There was no significant difference in all 3 adipocytokines between children with (4/20) and without coronary artery abnormalities (16/20). CONCLUSION Serum resistin levels were significantly elevated in patients with KD during the convalescent phase compared to controls. Serum leptin levels appeared to be higher in patients with KD, although the difference was not statistically significant. Adiponectin levels were similar in both cases and controls. Raised resistin and leptin levels may partially explain lipid perturbations observed during the convalescent phase of KD.
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Affiliation(s)
- Dibya Lochan Praharaj
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Amit Rawat
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Anju Gupta
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kanika Arora
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kumar Pilania
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sagar Bhattad
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Surjit Singh
- Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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Mahsa Mahmoudinezhad Dezfouli S, Salehi S, Khosravi S. Pathogenic and therapeutic roles of cytokines in Kawasaki diseases. Clin Chim Acta 2022; 532:21-28. [DOI: 10.1016/j.cca.2022.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/07/2022] [Accepted: 05/18/2022] [Indexed: 11/03/2022]
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Zdanowicz K, Bobrus-Chociej A, Lebensztejn DM. Chemerin as Potential Biomarker in Pediatric Diseases: A PRISMA-Compliant Study. Biomedicines 2022; 10:biomedicines10030591. [PMID: 35327393 PMCID: PMC8945351 DOI: 10.3390/biomedicines10030591] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 02/26/2022] [Accepted: 03/01/2022] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is the main source of adipokines and therefore serves not only as a storage organ, but also has an endocrine effect. Chemerin, produced mainly in adipocytes and liver, is a natural ligand for chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and C-C motif chemokine receptor-like 2 (CCRL2), which have been identified in many tissues and organs. The role of this protein is an active area of research, and recent analyses suggest that chemerin contributes to angiogenesis, adipogenesis, glucose homeostasis and energy metabolism. Many studies confirm that this molecule is associated with obesity in both children and adults. We conducted a systematic review of data from published studies evaluating chemerin in children with various disease entities. We searched PubMed to identify eligible studies published prior to February 2022. A total of 36 studies were selected for analysis after a detailed investigation, which was intended to leave only the research studies. Moreover, chemerin seems to play an important role in the development of cardiovascular and digestive diseases. The purpose of this review was to describe the latest advances in knowledge of the role of chemerin in the pathogenesis of various diseases from studies in pediatric patients. The mechanisms underlying the function of chemerin in various diseases in children are still being investigated, and growing evidence suggests that this adipokine may be a potential prognostic biomarker for a wide range of diseases.
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Garcia-Fandino R, Piñeiro Á. Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides? Front Immunol 2021; 11:610024. [PMID: 33552069 PMCID: PMC7862704 DOI: 10.3389/fimmu.2020.610024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/03/2020] [Indexed: 01/08/2023] Open
Abstract
In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the direct action of AMPs. In a scenario where most host cell membranes are dressed by a pathogenic lipid composition, AMPs can indiscriminately attack them. This is why we use the "AMP betrayal" term to describe this mechanism. Previously proposed cytokine/bradykinin storm mechanisms are not incompatible with this new proposal. Interestingly, the harmful action of AMPs could be prevented by new therapies aimed to reestablish the lipid composition or to inhibit the action of specific peptides.
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Affiliation(s)
- Rebeca Garcia-Fandino
- Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Ángel Piñeiro
- Departamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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9
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Giardullo L, Corrado A, Maruotti N, Cici D, Mansueto N, Cantatore FP. Adipokine role in physiopathology of inflammatory and degenerative musculoskeletal diseases. Int J Immunopathol Pharmacol 2021; 35:20587384211015034. [PMID: 33983056 PMCID: PMC8127732 DOI: 10.1177/20587384211015034] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 04/05/2021] [Indexed: 12/16/2022] Open
Abstract
We performed a systematic literature review to summarize the underlying pathogenic mechanisms by which adipokines influence rheumatological diseases and the resulting clinical manifestations. Increasing evidence display that numerous adipokines may significantly influence the development or clinical course of various rheumatological diseases. Despite the normal anti- or pro-inflammatory role of the cytokines, the serum level varies enormously in various rheumatological diseases. The expression of high levels of pro-inflammatory cytokines such as leptin or visfatin, respectively in systemic lupus erythematosus and in rheumatoid arthritis, represents a negative prognostic factor; other adipokines such as adiponectin, broadly known for their anti-inflammatory effects, showed a correlation with disease activity in rheumatoid arthritis. In the near future pro-inflammatory cytokines may represent a potential therapeutic target to restrain the severity of rheumatological diseases. Further studies on adipokines may provide important information on the pathogenesis of these diseases, which are not yet fully understood. The mechanisms by which adipokines induce, worsen, or suppress inflammatory and degenerative musculoskeletal pathologies and their clinical significance will be discussed in this review.
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Affiliation(s)
- Liberato Giardullo
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
| | - Addolorata Corrado
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
| | - Nicola Maruotti
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
| | - Daniela Cici
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
| | - Natalia Mansueto
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
| | - Francesco Paolo Cantatore
- Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical Sciences, University of Foggia, “Policlinico Riuniti” University Hospital, Foggia, Italy
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Li SC, Tsai KW, Huang LH, Weng KP, Chien KJ, Lin Y, Tu CY, Lin PH. Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration. Sci Rep 2020; 10:15645. [PMID: 32973234 PMCID: PMC7518260 DOI: 10.1038/s41598-020-72695-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 09/04/2020] [Indexed: 12/16/2022] Open
Abstract
Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD.
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Affiliation(s)
- Sung-Chou Li
- Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Wang Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Lien-Hung Huang
- Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ken-Pen Weng
- Congenital Structural Heart Disease Center, Department of Pediatrics, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan. .,Department of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
| | - Kuang-Jen Chien
- Congenital Structural Heart Disease Center, Department of Pediatrics, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan
| | - Yuyu Lin
- Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chi-Ying Tu
- Congenital Structural Heart Disease Center, Department of Pediatrics, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan
| | - Pei-Hsien Lin
- Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Cai X, Zhu Q, Wu T, Zhu B, Liu S, Liu S, Aierken X, Ahmat A, Li N. Association of circulating resistin and adiponectin levels with Kawasaki disease: A meta-analysis. Exp Ther Med 2019; 19:1033-1041. [PMID: 32010266 PMCID: PMC6966156 DOI: 10.3892/etm.2019.8306] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 11/05/2019] [Indexed: 12/12/2022] Open
Abstract
The present meta-analysis was performed to examine the association between circulating blood adipokine levels and Kawasaki disease (KD). Studies were identified by searching various databases, including Web of Science, EMBASE, PubMed, Wanfang and China National Knowledge Infrastructure. After the studies were pooled, the mean difference (MD) and corresponding 95% CI were calculated. Subgroup analyses and publication bias detection were also performed. The Cochrane Q test and I2 statistics were performed using Review Manager software (version 5.3) to test for heterogeneity. A Begg's test was used to assess publication bias and STATA software (version 12.0) was used for statistical analysis. The results revealed that the KD group exhibited higher levels of resistin compared with those in the healthy controls or disease controls (non-KD; MD=20.76, 95% CI=16.16-25.36, P<0.001; MD=21.27, 95% CI=14.24-28.29, P<0.001, respectively). In addition, when compared with those in patients exhibiting non-coronary artery lesions (NCAL), those with coronary artery lesions (CAL) had higher levels of adiponectin and resistin (MD=1.00, 95% CI=0.06-1.96, P=0.04; MD=2.77, 95% CI=1.32-4.22, P<0.001). Furthermore, compared with those in the inactive-phase group, patients in the active-phase group exhibited higher levels of resistin (MD=17.73, 95% CI=12.82-22.65, P<0.001). In conclusion, the present meta-analysis indicated that resistin levels were elevated in patients with KD. It was also revealed that circulating resistin and adiponectin levels in the CAL group were significantly increased compared with those in patients with NCAL. Furthermore, the active group had higher levels of resistin than the inactive group. The results of these meta-analyses indicated that resistin may serve an important role in the pathogenesis of KD and may therefore be used as biomarkers for the diagnosis of KD, whereas adiponectin may only serve an important role in the pathogenesis of CAL and may therefore be used as a biomarker to distinguish CAL from NCAL.
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Affiliation(s)
- Xintian Cai
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Qing Zhu
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Ting Wu
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Bin Zhu
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Shasha Liu
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Shanshan Liu
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Xiayire Aierken
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Ayguzal Ahmat
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
| | - Nanfang Li
- Center for Hypertension of The People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension Institute of Xinjiang, Urumqi, Xinjiang 830001, P.R. China
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