Hostname: page-component-55f67697df-4ks9w Total loading time: 0 Render date: 2025-05-09T10:55:29.907Z Has data issue: false hasContentIssue false
  • English
  • Français

Association of interleukin-35 polymorphisms with Kawasaki disease in Chinese children

Published online by Cambridge University Press:  08 May 2025

Jinhui Wu ,
Siqi Feng ,
Ya Su Open the ORCID record for Ya Su [Opens in a new window]  and
Qijian Yi Open the ORCID record for Qijian Yi [Opens in a new window]
Jinhui Wu
Affiliation:
Department of Cardiovascular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, National Clinical Research Center for Child Health and Disorders, National Clinical Key Cardiovascular Specialty, Children’s Hospital of Chongqing Medical University, Chongqing, China
Siqi Feng
Affiliation:
Department of Cardiovascular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, National Clinical Research Center for Child Health and Disorders, National Clinical Key Cardiovascular Specialty, Children’s Hospital of Chongqing Medical University, Chongqing, China
Ya Su*
Affiliation:
Department of Cardiovascular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, National Clinical Research Center for Child Health and Disorders, National Clinical Key Cardiovascular Specialty, Children’s Hospital of Chongqing Medical University, Chongqing, China
Qijian Yi*
Affiliation:
Department of Cardiovascular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Key Laboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health Commission, National Clinical Research Center for Child Health and Disorders, National Clinical Key Cardiovascular Specialty, Children’s Hospital of Chongqing Medical University, Chongqing, China
*
Corresponding authors: Ya Su; Email: [email protected], Qijian Yi; Email: [email protected]
Corresponding authors: Ya Su; Email: [email protected], Qijian Yi; Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Kawasaki disease is a leading cause of acquired heart disease in children in the developed world, characterised by acute systemic vasculitis, with a complex aetiology that remains poorly understood. Recent studies have highlighted the potential anti-inflammatory effects of Interleukin-35 in various proinflammatory and cardiovascular conditions. However, the relationship between Interleukin-35 gene polymorphisms and Kawasaki disease susceptibility, particularly in Chinese children, has not been well-explored.

In this study, we investigated the association between five Interleukin-35 single-nucleotide polymorphisms—rs2243115, rs2243123, rs583911, rs353698, and rs2302164—and Kawasaki disease in a cohort of Chinese children. A total of ninety-four Kawasaki disease patients and one hundred healthy controls were enrolled, with the Kawasaki disease patients further divided into subgroups based on the presence or absence of coronary artery lesions and incomplete or complete Kawasaki disease. Genotyping of Interleukin-35 polymorphisms was performed using the MassARRAY system.

The results showed the GT + GG genotypes and G allele of rs2243115 (T > G) were significantly more prevalent in Kawasaki disease patients with coronary artery lesions than in those without coronary artery lesions, suggesting a possible association with the development of coronary artery lesions. Additionally, the G allele of rs353698 (A > G) was more frequently observed in the incomplete Kawasaki disease group compared to the complete Kawasaki disease group, suggesting a possible association with the risk of incomplete Kawasaki disease.

Keywords

Coronary artery lesionskawasaki diseaseInterleukin-35single-nucleotide polymorphisms
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 7
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Newburger, JW, Takahashi, M, Gerber, MA, et al. Taubert, Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association, & American Academy of Pediatrics, Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 2004; 110: 2747–2771. doi: 10.1161/01.CIR.0000145143.19711.78.CrossRefGoogle Scholar
Sun, S-N, Zhou, Y, Fu, X, et al. A pilot study of the differentiated landscape of peripheral blood mononuclear cells from children with incomplete versus complete kawasaki disease. WJP 2024; 20: 189–200. doi: 10.1007/s12519-023-00752-4.Google ScholarPubMed
Kato, H, Koike, S, Yamamoto, M, Ito, Y, Yano, E. Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J Pediatr 1975; 86: 892–898. doi: 10.1016/s0022-3476(75)80220-4.CrossRefGoogle ScholarPubMed
Rowley, AH, Shulman, ST. Pathogenesis and management of kawasaki disease. Expert Rev Anti-INFE 2010; 8: 197–203. doi: 10.1586/eri.09.109.CrossRefGoogle ScholarPubMed
Su, Y, Feng, S, Luo, L, Liu, R, Yi, Q. Association between IL-35 and coronary arterial lesions in children with kawasaki disease. Clin Exp Med 2019; 19: 87–92. doi: 10.1007/s10238-018-0513-6.CrossRefGoogle ScholarPubMed
Vignali, DAA, Kuchroo, VK. IL-12 family cytokines: immunological playmakers. Nat Immunol 2012; 13: 722–728. doi: 10.1038/ni.2366.CrossRefGoogle ScholarPubMed
Li, X, Mai, J, Virtue, A, et al. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines. PloS One 2012; 7: e33628. doi: 10.1371/journal.pone.0033628.CrossRefGoogle ScholarPubMed
Collison, LW, Workman, CJ, Kuo, TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450: 566–569. doi: 10.1038/nature06306.CrossRefGoogle ScholarPubMed
Liu, J-Q, Liu, Z, Zhang, X, et al. Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis. J Immun (Baltimore, Md.: 1950) 2012; 188: 3099–3106. doi: 10.4049/jimmunol.1100106.Google ScholarPubMed
Bettini, M, Castellaw, AH, Lennon, GP, Burton, AR, Vignali, DAA. Prevention of autoimmune diabetes by ectopic pancreatic β-cell expression of interleukin-35. Diabetes 2012; 61: 1519–1526. doi: 10.2337/db11-0784.CrossRefGoogle ScholarPubMed
Lin, Y, Huang, Y, Lu, Z, et al. Decreased plasma IL-35 levels are related to the left ventricular ejection fraction in coronary artery diseases. PloS One 2012; 7: e52490. doi: 10.1371/journal.pone.0052490.CrossRefGoogle Scholar
Kempe, S, Heinz, P, Kokai, E, Devergne, O, Marx, N, Wirth, T. Epstein-barr virus-induced gene-3 is expressed in human atheroma plaques. Am J Pathol 2009; 175: 440–447. doi: 10.2353/ajpath.2009.080752.CrossRefGoogle ScholarPubMed
Guo, T, Yang, S, Liu, N, Wang, S, Cui, B, Ning, G. Association study of interleukin-12A gene polymorphisms with graves’ disease in two Chinese populations. Clin Endocrinol 2011; 74: 125–129. doi: 10.1111/j.1365-2265.2010.03905.x.CrossRefGoogle ScholarPubMed
Li, L-J, Pan, X-M, Sima, X, et al. Interactions of interleukin-12A and interleukin-12B polymorphisms on the risk of intracranial aneurysm. Mol Biol Rep 2012; 39: 11217–11223. doi: 10.1007/s11033-012-2031-z.CrossRefGoogle ScholarPubMed
Posadas-Sánchez, R, Pérez-Hernández, N, Angeles-Martínez, J, et al. Interleukin 35 polymorphisms are associated with decreased risk of premature coronary artery disease, metabolic parameters, and IL-35 levels: the genetics of atherosclerotic disease (GEA) study. Mediat Inflamm 2017; 2017: 6012795. doi: 10.1155/2017/6012795.CrossRefGoogle ScholarPubMed
Japan Kawasaki Disease Research Committee. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Tokyo: Ministry of Health and Welfare; 1984, 1–10. http://www.niph.go.jp/wadai/mhlw/1984/s5906011pdf.Google Scholar
Nakano, H, Ueda, K, Saito, A, Nojima, K. Repeated quantitative angiograms in coronary arterial aneurysm in kawasaki disease. Am J Cardiol 1985; 56: 846–851. doi: 10.1016/0002-9149(85)90767-2.CrossRefGoogle ScholarPubMed
Shen, L, Zhang, H, Zhou, X, Liu, R. Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population. Cytokine 2015; 76: 363–367. doi: 10.1016/j.cyto.2015.09.007.CrossRefGoogle ScholarPubMed
Namkung, J-H, Lee, J-E, Kim, E, et al. Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL-12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic dermatitis in Koreans. J Dermatol Sci 2010; 57: 199–206. doi: 10.1016/j.jdermsci.2009.12.003.CrossRefGoogle Scholar
Lin, Y, Xue, Y, Huang, X, et al. Association between interleukin-35 polymorphisms and coronary heart disease in the Chinese zhuang population: a case-control study. Coronary Artery Dis 2018; 29: 423–428. doi: 10.1097/MCA.0000000000000635.CrossRefGoogle ScholarPubMed
Zhang, Y, Duan, S, Wei, X, Zhao, Y, Zhao, L, Zhang, L. Association between polymorphisms in FOXP3 and EBI3 genes and the risk for development of allergic rhinitis in Chinese subjects. Hum Immunol 2012; 73: 939–945. doi: 10.1016/j.humimm.2012.07.319.CrossRefGoogle ScholarPubMed
Zheng, R, Liu, H, Song, P, et al. Epstein-barr virus-induced gene 3 (EBI3) polymorphisms and expression are associated with susceptibility to pulmonary tuberculosis. Tuberculosis (Edinburgh, Scotland) 2015; 95: 497–504. doi: 10.1016/j.tube.2015.03.009.CrossRefGoogle ScholarPubMed
Guan, S-Y, Liu, L-N, Mao, Y-M, et al. Association between Interleukin 35 gene single nucleotide polymorphisms and systemic lupus erythematosus in a Chinese han population. Biomolecules 2019; 9: 157. doi: 10.3390/biom9040157.CrossRefGoogle ScholarPubMed
Li, H, Liu, Y-X, Huang, J-Y, Zhu, Y-F, Wang, K. Analysis for interaction between interleukin-35 genes polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese han population. Bmc Cardiovasc Disor 2021; 21: 6. doi: 10.1186/s12872-020-01811-8.CrossRefGoogle ScholarPubMed
Buda, P, Friedman-Gruszczyńska, J, Książyk, J. Anti-inflammatory treatment of kawasaki disease: comparison of current guidelines and perspectives. Front Med 2021; 8: 738850. doi: 10.3389/fmed.2021.738850.CrossRefGoogle Scholar
Li, H, Xing, H. Interleukin-35 enhances regulatory T cell function by potentially suppressing their transdifferentiation into a T helper 17-like phenotype in kawasaki disease. Immunol Invest 2023; 52: 513–528. doi: 10.1080/08820139.2023.2201283.CrossRefGoogle Scholar
Sun, M, Xing, H. Interleukin-35 regulates peripheral T cell activity in patients with kawasaki disease. Int Immunopharmacol 2021; 96: 107642. doi: 10.1016/j.intimp.2021.107642.CrossRefGoogle ScholarPubMed
Sima, X, Xu, J, Li, Q, Luo, L, Liu, J, You, C. Gene-gene interactions between interleukin-12A and interleukin-12B with the risk of brain tumor. Dna Cell Biol 2012; 31: 219–223. doi: 10.1089/dna.2011.1331.CrossRefGoogle ScholarPubMed
An, HS, Kim, GB, Song, MK, et al. The occurrence of coronary artery lesions in kawasaki disease based on C-reactive protein levels: a retrospective cohort study. Pediatr Rheumatol Online J 2021; 19: 78. doi: 10.1186/s12969-021-00566-6.CrossRefGoogle ScholarPubMed
Qiu, H, He, Y, Rong, X, et al. Delayed intravenous immunoglobulin treatment increased the risk of coronary artery lesions in children with kawasaki disease at different status. Postgrad Med 2018; 130: 442–447. doi: 10.1080/00325481.2018.1468712.CrossRefGoogle ScholarPubMed
Bal, AK, Prasad, D, Umali Pamintuan, MA, Mammen-Prasad, E, Petrova, A. Timing of intravenous immunoglobulin treatment and risk of coronary artery abnormalities in children with kawasaki disease. Pediatr Neonatol 2014; 55: 387–392. doi: 10.1016/j.pedneo.2013.11.007.CrossRefGoogle ScholarPubMed
Liu, R, Gao, F, Huo, J, Yi, Q. Study on the relationship between mean platelet volume and platelet distribution width with coronary artery lesion in children with kawasaki disease. Platelets 2012; 23: 11–16. doi: 10.3109/09537104.2011.586073.CrossRefGoogle Scholar