ArticlePloS one2014
Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Targeting the NLRP3 inflammasome in rheumatoid arthritis fibroblast-like synoviocytes: pathogenic mechanisms, therapeutic strategies, and translational perspectives.Frontiers in pharmacology · 2026Review
- Association of NLRP3 single nucleotide polymorphisms with juvenile idiopathic arthritis: a case-control study.Clinical rheumatology · 2025Article
- Natural compound library screening to identify berberine as a treatment for rheumatoid arthritis.Clinical rheumatology · 2024Article
- The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review.International journal of molecular sciences · 2024Review
- Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry.Rheumatology and therapy · 2023Article
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- Article
- NLRP3 Gene Polymorphisms in Rheumatoid Arthritis and Primary Sjogren's Syndrome Patients.Diagnostics (Basel, Switzerland) · 2023Article
- The regulation of self-tolerance and the role of inflammasome molecules.Frontiers in immunology · 2023Review
- Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search.Rheumatology (Oxford, England) · 2022Review
- Gene Ontology Analysis Highlights Biological Processes Influencing Non-Response to Anti-TNF Therapy in Rheumatoid Arthritis.Biomedicines · 2022Article
- Role of NLRP3 Inflammasome in Rheumatoid Arthritis.Frontiers in immunology · 2022Review
- Pharmacogenetics of Drug Therapies in Rheumatoid Arthritis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Anti-inflammatory and Immunomodulatory Therapies in Atherosclerosis.Handbook of experimental pharmacology · 2022Review
- CARD8 SNP rs11672725 Identified as a Potential Genetic Variant for Adult-Onset Still's Disease.Life (Basel, Switzerland) · 2021Article
- Inflammasome and Its Therapeutic Targeting in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene: results from a multicentre study of four European psoriasis cohorts.Journal of the European Academy of Dermatology and Venereology : JEADV · 2020Article
- Crosstalk Between Gut Microbiota and Innate Immunity and Its Implication in Autoimmune Diseases.Frontiers in immunology · 2020Review
- Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and -609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related toBioMed research international · 2020Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMany patients with rheumatoid arthritis (RA) benefit from tumor necrosis factor-α blocking treatment (anti-TNF), but about one third do not respond. The objective of this study was to replicate and extend previously found associations between anti-TNF treatment response and genetic variation in the TNF-, NF-κB- and pattern recognition receptor signalling pathways.
methodsForty-one single nucleotide polymorphisms (SNPs), including 34 functional, in 28 genes involved in inflammatory pathways were assessed in 538 anti-TNF naive Danish RA patients with clinical data. Multivariable logistic regression analyses were performed to test associations between genotypes and treatment response at 3-6 months using the European League Against Rheumatism (EULAR) response criterion. American College of Rheumatology treatment response (ACR50) and relative change in 28-joint disease activity score (relDAS28) were used as secondary outcomes. Subgroup analyses were stratified according to smoking status, type of anti-TNF drug and IgM-Rheumatoid Factor (IgM-RF) status. False discovery rate (FDR) controlling was used to adjust for multiple testing.
resultsStatistically significant associations with EULAR response were found for two SNPs in NLRP3(rs4612666) (OR (odds ratio) for good/moderate response = 0.64 (95% confidence interval: 0.44-0.95), p = 0.025, q = 0.95) and INFG(rs2430561) (OR = 0.40 (0.21-0.76), p = 0.005, q = 0.18) and among IgM-RF positive patients for TNFRS1A(rs4149570) (0.59 (0.36-0.98), p = 0.040, q = 0.76). Current smokers who carried the NLRP3(rs4612666) variant allele were less likely to benefit from anti-TNF treatment (OR = 0.24 (0.10-0.56), p = 0.001, q = 0.04).
conclusionsIn a population of Danish RA patients, we confirm the NLRP3 gene as associated with EULAR anti-TNF response as previously reported. The NLRP3 variant (T) allele is associated with lower treatment response, in particular among current smokers. Furthermore, we find that a functional polymorphism in the interferon-γ gene is associated with anti-TNF response. All findings should be tested by replication in independent validation cohorts and augmented by assessing cytokine levels and activities of the relevant gene products.
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