Association of the IL16 Asn1147Lys polymorphism with intravenous immunoglobulin resistance in Kawasaki disease

Kim, Hea-Ji; Kim, Jae-Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung-Yil; Kil, Hong Ryang; Kim, Jun Seok; Han, Myung-Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Hong, Young Mi; Jang, Gi Young; Lee, Jong-Keuk

doi:10.1038/s10038-020-0721-2

Cited by 6 publications

(7 citation statements)

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“…The incidence of resistance to IVIG is generally reported in the literature between 10-20% [14][15][16]. Classi cation of patients according to the risk of IVIG resistance could inform decisions to administer more aggressive initial treatment, with the aim of reducing the risk of coronary artery lesion development [10].…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

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Bilgüvar

et al. 2022

Preprint

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Background Kawasaki disease (CD) is an acute febrile systemic vasculitis that is the most common cause of coronary artery aneurysm (CAA) in children. Resistance to IVIG, which is used to reduce the risk of developing CAA, is an important risk factor, and risk scoring systems used to predict the development of this resistance gave different results in different breeds. We planned our study to investigate the effect of genetic factors on the development of IVIG resistance. Methods Patients diagnosed with CD by whole exome gene analysis were analyzed retrospectively. Blood samples were obtained from a randomized subgroup (n:97). Previously reported IVIG resistance-associated exonic SNPs at five different gene loci (IL16,TNFSF14, NFATC2,DERL3,SAMD9L) were evaluated by whole-exome sequencing(WES). Results 259 patients (male/female: 1.67) with CD were included in the study. The rates of CAA and IVIG resistance in our patients were 11.6% and 21.6%, respectively. The risk of developing CAA was significantly increased in patients with IVIG resistance (p < 0.001). As a result, IVIG resistance frequency increased in the presence of three SNPs (the IL16,TNFSF14, NFATC2 genes, respectively). Conclusion The development of resistance at different rates in different races against IVIG, which is used in the treatment of CD, has led to genetic studies. In our study, we found mutations in three genes (IL16, TNFSF14, NFATC) that play a role in T lymphocyte activation in patients with IVIG resistance. We think that the role of genetic factors in the resistance mechanism will become clear with the increase in genetic studies to be done.

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Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

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Bilgüvar

et al. 2022

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“…Alternatively, numerous coding variants of interleukins and relevant receptors have been associated with IVIG resistance. 46,47 Therefore, genome-wide association studies may provide insight into risk factors associated with IVIG treatment resistance in MG patients. 48 Similarly, serum cytokine profiles may prove helpful in predicting poor response to IVIG, as post-IVIG levels of IL-6 and IL-10 were found to be significantly higher in non-responders than in responders in patients with Kawasaki disease.…”

Section: Discussionmentioning

confidence: 99%

VNTR2/VNTR3 genotype in the FCGRT gene is associated with reduced effectiveness of intravenous immunoglobulin in patients with myasthenia gravis

Liu

Zhang

et al. 2021

Ther Adv Neurol Disord

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Background: Intravenous immunoglobulin (IVIG) has been commonly used to treat myasthenia gravis exacerbation, but is still ineffective in nearly 30% of patients. A variable number of tandem repeat (VNTR) polymorphism in the FCGRT gene has been found to reduce the efficiency of IgG biologics. However, whether the polymorphism influences the efficacy of IVIG in generalized myasthenia gravis (MG) patients with exacerbations remains unknown. Methods: The distribution of VNTR genotypes was analyzed in 334 patients with MG. Varied VNTR alleles were determined by capillary electrophoresis and confirmed by Sanger sequencing. Information of endogenous IgG levels were collected in patients without previous immunotherapy ( n = 26). Medical records of patients who received IVIG therapy were retrospectively analyzed for therapeutic outcomes of IVIG treatment ( n = 61). Patients whose Activities of Daily Living scores decreased by 2 or more points on day 14 were considered responders to the treatment. Results: The VNTR3/3 and VNTR2/3 genotypes were detected in 96.7% (323/334) and 3.4% (11/334) patients, respectively. Patients with VNTR2/3 heterozygosity had lower endogenous IgG levels than those with VNTR3/3 homozygosity (9.81 ± 2.61 g/L versus 12.41 ± 2.45g/L, p = 0.016). The response rate of IVIG therapy was 78.7% (48/61). All responders and nine non-responders were VNTR3/3 homozygotes, whereas all the patients with VNTR2/3 genotypes were non-responders ( n = 4). In patients who took IVIG treatments, endogenous IgG levels were significantly lower in non-responders compared with responders (12.93 ± 2.24 g/L versus 8.85 ± 2.69 g/L, p = 0.006), especially in VNTR2/3 heterozygotes (7.86 ± 1.78 g/L, p = 0.001). Conclusion: The VNTR2/3 genotype could influence endogenous IgG levels and serve as a predictive marker for poor responses to IVIG in MG patients.

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“…SNPs in ve different gene loci (IL16, TNFSF14, NFATC2, DERL3, SAMD9L) identi ed by recent study related to IVIG resistance were examined. 10 Data were analyzed using (SPSS Statistics for Macintosh, version 24.0; IBM Corp., Armonk, NY, USA). Categorical variables were summarized using frequencies (percentage [%]).…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

“…[14][15][16] Classi cation of patients according to the risk of IVIG resistance could inform decisions to administer more aggressive initial treatment, with the aim of reducing the risk of coronary artery lesion development. 10 Many risk scoring systems have been developed so far with the idea of coronary complications can be reduced by using aggressive treatment regimens in the early period if the response to treatment can be predicted at the beginning of the disease. [6][7][8][9] These scoring systems, which were developed based on clinical ndings and laboratory parameters, have not been widely used worldwide since their prediction power varies according to the population they are applied to.…”

Section: It Has Been Reported That the Probability Of Developing Coronary Artery Lesions Decreases With High Dose Ivigmentioning

confidence: 99%

“…The diseases associated with IL-16 are bronchial asthma, 27 Crohn's disease 28 , systemic lupus erythematosus, 29 rheumatoid arthritis, 30 and multiple myeloma. 31 IL16 variant of "rs11556218 (T / G)" identi ed by Kim et al 10 On IVIG resistance in IL16 gene in KD was associated with a predisposition to multiple sclerosis. 32 TNFSF14 gene encodes one of the tumor necrosis factor (TNF) ligands.…”

Section: It Has Been Reported That the Probability Of Developing Coronary Artery Lesions Decreases With High Dose Ivigmentioning

confidence: 99%

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Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

Varlı

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Bilgüvar

et al. 2021

Preprint

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Objective Kawasaki disease (KD) is an acute febrile systemic vasculitis and the most common cause of coronary artery aneurysm (CAA) in children. Intravenous immunoglobulin (IVIG) therapy is used to prevent fever and systemic inflammation. However, IVIG resistance is the most important risk factor of morbidity and mortality. It has been identified several single nucleotide polymorphisms (SNPs) related to IVIG resistance and this research aims to analyze these polymorphisms in our study population. Methods Patients diagnosed with KD (n:259) were analyzed retrospectively. Blood samples were taken from a randomized subgroup (n:97). Previously reported IVIG resistance related exonic SNPs at five different gene loci (IL16, TNFSF14, NFATC2, DERL3, SAMD9L) were evaluated by whole exome sequencing (WES). Results Between 2010–2019, 259 patients (male/female: 1,67) with KD were submitted to our clinic. CAA and IVIG resistance rates were 11.6% and 21.6%, respectively. The risk of developing CAA was significantly increased in patients with IVIG resistance (p < 0.001). As a result, IVIG resistance frequency increased in the presence of three SNPs. These are "rs11556218"(p.Asn1147Lys), "rs344560"(p.Lys214Glu), "rs12479626"(p.His446Arg), and are located in IL16, TNFSF14, NFATC2 genes, respectively. Conclusions Until now, KD-related genetic data mostly obtained from studies involving large cohorts from Northeast Asian countries. In the analysis of this largest Turkish cohort in the literature, we found that, similar with previous studies, the IL16 gene may be plays important role in the IVIG resistance mechanism.

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Association of the IL16 Asn1147Lys polymorphism with intravenous immunoglobulin resistance in Kawasaki disease

Cited by 6 publications

References 33 publications

Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

VNTR2/VNTR3 genotype in the FCGRT gene is associated with reduced effectiveness of intravenous immunoglobulin in patients with myasthenia gravis

Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

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