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Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

ABSTRACT: Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

SUBMITTER: Prieto-Pena D

PROVIDER: S-EPMC8352942 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

Prieto-Peña Diana D Remuzgo-Martínez Sara S Genre Fernanda F Pulito-Cueto Verónica V Atienza-Mateo Belén B Llorca Javier J Sevilla-Pérez Belén B Ortego-Centeno Norberto N Marquez Ana A Lera-Gómez Leticia L Leonardo María Teresa MT Peñalba Ana A Narváez Javier J Martín-Penagos Luis L Rodrigo Emilio E Miranda-Filloy José A JA Caminal-Montero Luis L Collado Paz P Sánchez Pérez Javier J de Argila Diego D Rubio Esteban E León Luque Manuel M Blanco-Madrigal Juan María JM Galíndez-Agirregoikoa Eva E Gualillo Oreste O Martín Javier J Castañeda Santos S Blanco Ricardo R González-Gay Miguel A MA López-Mejías Raquel R

Scientific reports 20210809 1

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, r ...[more]

PMID: 34373564

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Project description:The Interleukin (IL)-33 is important in several inflammatory diseases and its cellular receptor is the Interleukin 1 receptor-like 1 (IL1RL1), also called suppression of tumorigenicity 2 ligand (ST2L). This study investigated associations between single nucleotide variants (SNVs) in the IL33 gene and in the IL1RL1 (ST2) gene with periodontitis. Additionally, aimed to determine the role of Aggregatibacter actinomycetemcomitans (Aa) relative amount in the subgingival biofilm in these associations. A cross-sectional study was carried out with 506 individuals that answered a structured questionnaire used to collect their health status, socioeconomic-demographic, and behavioral characteristics. Periodontal examination was performed to determine the presence and severity of periodontitis, and subgingival biofilm samples were collected to quantify the relative amount of Aa by real time polymerase chain reaction. Human genomic DNA was extracted from whole blood cells and SNV genotyping was performed. Logistic regression estimated the association measurements, odds ratio (OR), and 95% confidence interval (95%CI), between the IL33 and ST2 genes with periodontitis, and subgroup analyses assessed the relative amount of Aa in these associations. 23% of individuals had periodontitis. Adjusted measurements showed a statistically significant inverse association between two SNVs of the ST2; rs148548829 (C allele) and rs10206753 (G allele). These two alleles together with a third SNV, the rs11693204 (A allele), were inversely associated with moderate periodontitis. One SNV of the IL33 gene also showed a statistically significant inverse association with moderate periodontitis. Nine SNVs of the ST2 gene were inversely associated with the relative amount of Aa. In the high Aa subgroup, there was a direct association between 11 SNVs of the ST2 gene and moderate periodontitis and two SNVs of the ST2 gene and severe periodontitis, and eight SNVs of the ST2 gene and periodontitis. These exploratory findings of genetic variants in IL-33/ST2 axis support the concept that the different tissue responses among individuals with periodontitis may be modulated by the host's genetics, influencing the physiopathology of the disease.

Dataset Information

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

Publications

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

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