ArticlePloS one2012
PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Enhancement of activation-induced T cell proliferation by SIRPG in a CD47-independent manner.Frontiers in immunology · 2025Article
- Risk Allele rs117026326-Mediated Alternative Splicing of GTF2I Promotes B Cell Proliferation in Primary Sjögren's Syndrome.Journal of immunology research · 2025Article
- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Analysis ofDiagnostics (Basel, Switzerland) · 2023Article
- Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn's disease.Clinical and experimental immunology · 2022Article
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- Splicing machinery is impaired in rheumatoid arthritis, associated with disease activity and modulated by anti-TNF therapy.Annals of the rheumatic diseases · 2022Article
- Overexpression of theJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Differential impacts of TNFα inhibitors on the transcriptome of Th cells.Arthritis research & therapy · 2021Article
- Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.Frontiers in immunology · 2021Review
- Influence ofFrontiers in immunology · 2021Review
- Non-receptor tyrosine kinase signaling in autoimmunity and therapeutic implications.Pharmacology & therapeutics · 2019Review
- Utilizing a PTPN22 gene signature to predict response to targeted therapies in rheumatoid arthritis.Journal of autoimmunity · 2019Article
- Crispr/Cas Mediated Deletion of PTPN22 in Jurkat T Cells Enhances TCR Signaling and Production of IL-2.Frontiers in immunology · 2018Article
- Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis.Scientific reports · 2017Article
- Citrullination of NF-κB p65 promotes its nuclear localization and TLR-induced expression of IL-1β and TNFα.Science immunology · 2017Article
- A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22.JCI insight · 2016Article
- Article
- Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics.Immunologic research · 2014Review
- PTPN22: the archetypal non-HLA autoimmunity gene.Nature reviews. Rheumatology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
PTPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease. The effect of the R-to-W conversion on the phosphatase activity of PTPN22 protein and the impact of the minor T allele of the C1858T SNP on the activation of T cells has remained controversial. In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood. Here we report the identification of an alternative splice form of human PTPN22, namely PTPN22.6. It lacks the nearly entire phosphatase domain and can function as a dominant negative isoform of the full length PTPN22. Although conversion of R620 to W620 in the context of PTPN22.1 attenuated T cell activation, expression of the tryptophan variant of PTPN22.6 reciprocally led to hyperactivation of human T cells. More importantly, the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis. Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.