Abstract
Inflammasome is the cytoplasmic complex responsible for pro-IL1 β cleavage and secretion of IL-1β. Recently our group reported the first association between polymorphisms in the inflammasome receptor NLRP1 and adult-onset systemic lupus erythematosus (SLE) "di per se" and especially in SLE-associated renal disease, suggesting the involvement of NLRP1-inflammasome in the immune dysregulation characteristic of SLE patients. Considering that juvenile-onset SLE (JSLE) is more severe than adult SLE, and that the genetic background plays a major role in the early development of autoimmune diseases, we analysed selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, IL1B, TNFAIP3) of children and adolescents with JSLE (n = 90) and in healthy controls (n = 144). A single polymorphism in IL1B, and not NLRP1, gene resulted in association with JSLE, suggesting that IL-1 β is involved in the pathogenesis of SLE, but different genes could play specific role in adult- or early-onset disease.
Keywords:
Genetic background; IL-1β; inflammasome; juvenile systemic lupus erythematosus; single nucleotide polymorphisms.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Adolescent
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Adult
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Age of Onset
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Alleles
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / immunology
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CARD Signaling Adaptor Proteins / genetics
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CARD Signaling Adaptor Proteins / immunology
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Case-Control Studies
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Child
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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Female
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Gene Expression
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Gene Frequency
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Genetic Predisposition to Disease*
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Haplotypes
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Humans
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Inflammasomes / genetics
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Inflammasomes / immunology
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Interleukin-1beta / genetics*
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Interleukin-1beta / immunology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / immunology
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Lupus Erythematosus, Systemic / genetics*
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / pathology
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Male
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLR Proteins
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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Polymorphism, Single Nucleotide
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Tumor Necrosis Factor alpha-Induced Protein 3
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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CARD Signaling Adaptor Proteins
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CARD8 protein, human
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Carrier Proteins
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DNA-Binding Proteins
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Inflammasomes
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Interleukin-1beta
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Intracellular Signaling Peptides and Proteins
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLR Proteins
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NLRP1 protein, human
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NLRP3 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3