IL10 Family Member Genes IL19 and IL20 Are Associated With Recurrent Wheeze After Respiratory Syncytial Virus Bronchiolitis

Ermers, Marieke J. J.; Janssen, Riny; Onland‐Moret, N. Charlotte; Hodemaekers, Hennie M.; Rovers, Maroeska M.; Houben, Michiel L.; Kimpen, Jan L. L.; Bont, Louis

doi:10.1203/pdr.0b013e31822f5863

Cited by 26 publications

(24 citation statements)

References 36 publications

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“…The IL8 polymorphism was not shown to be related to either early or late wheezing after RSV LRTI in this study [75]; however, it was found to be related to wheezing and RSV LRTI in a study by Goetghebuer et al [77]. In a subsequent study by Ermers et al [76], the genetic variation in adaptive immunity genes, and particularly in IL10 family member genes IL19 and IL20 genes, seemed to be associated with recurrent wheeze after RSV LRTI, and perhaps infant wheeze in the general population. This suggests a role for IL19 and IL20 cytokines in airway disease.…”

Section: Resultsmentioning

confidence: 65%

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

et al. 2017

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IntroductionThe REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. The objective of this fifth publication was to determine the long-term respiratory morbidity associated with RSV lower respiratory tract infection (RSV LRTI) in early life.MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. This was supplemented by inclusion of papers published whilst drafting the manuscript. Studies reporting data on the incidence and long-term wheezing and asthma following RSV LRTI in early life were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.ResultsA total of 2337 studies were identified of which 74 were included. Prospective, epidemiologic studies consistently demonstrated that RSV LRTI is a significant risk factor for on-going respiratory morbidity characterized by transient early wheezing and recurrent wheezing and asthma within the first decade of life and possibly into adolescence and adulthood (high SOE). RSV LRTI was also associated with impaired lung function in these children (high SOE). Respiratory morbidity has been shown to result in reduced quality of life and increased healthcare resource use (moderate SOE). The mechanisms through which RSV contributes to wheezing/asthma development are not fully understood, but appear to relate to the viral injury, preexisting abnormal lung function and/or other factors that predispose to wheezing/asthma, including genetic susceptibility, altered immunology, eosinophilia, and associated risk factors such as exposure to environmental tobacco smoke (high SOE).ConclusionThere is growing evidence that RSV LRTI in early childhood is associated with long-term wheezing and asthma and impaired lung function. Future research should aim to fully elucidate the pathophysiological mechanisms through which RSV causes recurrent wheezing/asthma.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-017-0151-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 65%

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

et al. 2017

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“…However, the IL20 rs2981573 genetic variant has been reported to be associated with several inflammatory diseases. The minor allele frequency was found to be lower than that of healthy controls in patients with ulcerative colitis in a Mexican population [30], in patients with recurrent wheeze after respiratory syncytial bronchiolitis in a Dutch population [10], and in patients with palmoplantar pustulosis in an Estonian (Caucasian) population [31].…”

Section: Discussionmentioning

confidence: 87%

“…Second, according to the lowest p value in the initial test on 13 SNPs, we focused on IL20 rs2981573. There is linkage disequilibrium between IL20 rs2981573, IL19 rs2243191, and IL19 rs2243188 in individuals of European ancestry [10]. Thus, whether IL20 rs2981573 was the functional SNP or another SNP was in linkage disequilibrium with the causal SNP was not determined.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no report of a genetic association of the IL19, IL20, and IL24 variants with septic shock. A genetic association study focusing on this gene cluster found associations of IL19 and IL20 SNPs with recurrent wheeze after respiratory syncytial virus bronchiolitis [10]. There is also increasing evidence that IL19 and IL20 SNPs are associated with the development of inflammatory diseases such as ulcerative colitis [9] and systemic juvenile idiopathic arthritis [11].…”

Section: Introductionmentioning

confidence: 99%

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The<b><i> IL20</i></b> Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock

et al. 2018

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Background: The IL10 family of genes includes crucial immune regulators.We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock. Methods: Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality. Results: Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10^-4). Patients with the GG genotype had more organ dysfunction (p < 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032). Conclusions: The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.

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“…One study demonstrated significant associations with wheezing in the 15 months after RSV LRI ( IL19, IL20, MUC5AC, TNFRSF1B, C3, CTLA4, CXCL9, IL4R and IL7 ) [124], of which C3, CTLA4 and IL4R overlap with variants identified with asthma [125–129]. They also identified a functional SNP in IL13 associated with 6-year wheezing outcomes (n = 72) after RSV LRI [130], which has replicated inconsistently in studies of asthma [125].…”

Section: Status Of Current Genetic Knowledge On Shared Genes For Rsv mentioning

confidence: 99%

Genes Associated with RSV Lower Respiratory Tract Infection and Asthma: The Application of Genetic Epidemiological Methods to Understand Causality

Larkin

Hartert

2015

Future Virol.

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Infants with respiratory syncytial virus (RSV) lower respiratory tract infections (LRIs) are at increased risk for childhood asthma. The objectives of this article are to review the genes associated with both RSV LRI and asthma, review analytic approaches to assessing shared genetic risk and propose a future perspective on how these approaches can help us to understand the role of infant RSV infection as both an important risk factor for asthma and marker of shared genetic etiology between the two conditions. The review of shared genes and thus pathways associated with severity of response to RSV infection and asthma risk can help us to understand mechanisms of disease and ultimately propose new and novel targets for primary prevention of both diseases.

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IL10 Family Member Genes IL19 and IL20 Are Associated With Recurrent Wheeze After Respiratory Syncytial Virus Bronchiolitis

Cited by 26 publications

References 36 publications

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood

The<b><i> IL20</i></b> Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock

Genes Associated with RSV Lower Respiratory Tract Infection and Asthma: The Application of Genetic Epidemiological Methods to Understand Causality

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