ArticleArthritis research & therapy2013
Epistasis with HLA DR3 implicates the P2X7 receptor in the pathogenesis of primary Sjögren's syndrome.
Article in Arthritis research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- P2X7R of synovial fibroblasts is a potential therapeutic target associated with refractory rheumatoid arthritis.Science advances · 2026Article
- The P2X7 Receptor in Autoimmunity.International journal of molecular sciences · 2023Review
- Purinergic Signaling in Oral Tissues.International journal of molecular sciences · 2022Review
- Analysis of the saliva metabolic signature in patients with primary Sjögren's syndrome.PloS one · 2022Article
- Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren's Syndrome.Journal of clinical medicine · 2021Review
- P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.Frontiers in pharmacology · 2020Review
- Update on Pathogenesis of Sjogren's Syndrome.Current rheumatology reviews · 2017Review
- Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells.Immunology and cell biology · 2015Article
- Alum, an aluminum-based adjuvant, induces Sjögren's syndrome-like disorder in mice.Clinical and experimental rheumatologyArticle
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionThe aim of this study was to examine the association between functional polymorphisms in the pro-inflammatory P2X7 receptor and the Ro/La autoantibody response in primary Sjögren's syndrome (pSS).
methodsTwelve functional P2RX7 polymorphisms were genotyped in 114 pSS patients fulfilling the Revised American-European Consensus Criteria for pSS, and 136 controls. Genotyping of the A1405G (rs2230912) polymorphism was performed on a replication cohort consisting of 281 pSS patients and 534 controls. P2X7 receptor function in lymphocytes and monocytes was assessed by measurement of ATP-induced ethidium+ uptake. Serum IL-18 levels were determined by ELISA.
resultsThe minor allele of P2RX7 A1405G is a tag for a common haplotype associated with gain in receptor function, as assessed by ATP-induced ethidium+ uptake. A positive association between 1405G and anti-Ro±La seropositive pSS patients was observed in Cohort 1. Although not replicated in Cohort 2, there was a consistent, significant, negative epistatic interaction effect with HLA-DR3 in seropositive pSS patients from both cohorts, thereby implicating this gain of function variant in the pathogenesis of pSS. Serum IL-18 was elevated in seropositive pSS patients, but was not influenced by P2RX7 A1405G.
conclusionsThe P2RX7 1405G gain-of-function haplotype may be a risk factor for seropositive pSS in a subset of subjects who do not carry HLA risk alleles, but has no effect in subjects who do (epistasis). Potential mechanisms relate to autoantigen exposure and inflammatory cytokine expression. The observed elevation of IL-18 levels is consistent with P2X7 receptor activation in seropositive pSS patients. Collectively these findings implicate P2X7 receptor function in the pathogenesis of pSS.
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