ArticlePloS one2012
High basal activity of the PTPN22 gain-of-function variant blunts leukocyte responsiveness negatively affecting IL-10 production in ANCA vasculitis.
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 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.The Journal of rheumatology · 2015Pooled it
- The protein tyrosine phosphatase Lyp/PTPN22 drives TNFα-induced priming of superoxide anions production by neutrophils and arthritis.Free radical biology & medicine · 2025Article
- Genome-wide prediction of pathogenic gain- and loss-of-function variants from ensemble learning of a diverse feature set.Genome medicine · 2023Article
- New Insights into Pathogenesis and Treatment of ANCA-Associated Vasculitis: Autoantibodies and Beyond.Antibodies (Basel, Switzerland) · 2023Review
- Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis.Rheumatology and immunology research · 2023Review
- The genomic landscape of ANCA-associated vasculitis: Distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus.Frontiers in immunology · 2023Article
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.Scientific reports · 2022Article
- Epidemiology and genetics of granulomatosis with polyangiitis.Rheumatology international · 2021Review
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- The Contribution of PTPN22 to Rheumatic Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2019Review
- Association of PTPN22 1858C/T Polymorphism with Autoimmune Diseases: A Systematic Review and Bayesian Approach.Journal of clinical medicine · 2019Article
- Pathogenesis and therapeutic interventions for ANCA-associated vasculitis.Nature reviews. Rheumatology · 2019Review
- Current State of Precision Medicine in Primary Systemic Vasculitides.Frontiers in immunology · 2019Review
- Regulation of autoimmune and anti-tumour T-cell responses by PTPN22.Immunology · 2018Review
- Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides.Frontiers in immunology · 2018Review
- Article
- Histone modification signature at myeloperoxidase and proteinase 3 in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis.Clinical epigenetics · 2016Article
- The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human.Journal of immunology (Baltimore, Md. : 1950) · 2015Review
- Autoimmunity-associated LYP-W620 does not impair thymic negative selection of autoreactive T cells.PloS one · 2014Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Consequences of expression of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gain-of-function variant were evaluated in leukocytes from patients with anti-neutrophil cytoplasmic autoantibody (ANCA) disease. The frequency of the gain-of-function allele within the Caucasian patient cohort was 22% (OR 1.45), compared to general American Caucasian population (16.5%, p = 0.03). Examination of the basal phosphatase activity of PTPN22 gain-of-function protein indicated persistently elevated activity in un-stimulated peripheral leukocytes, while basal activity was undetectable in leukocytes from patients without the gain-of-function variant. To examine consequences of persistently high PTPN22 activity, the activation status of ERK and p38 MAPK were analyzed. While moderate levels of activated ERK were observed in controls, it was undetectable in leukocytes expressing PTPN22 gain-of-function protein and instead p38MAPK was up-regulated. IL-10 transcription, reliant on the ERK pathway, was negatively affected. Over the course of disease, patients expressing variant PTPN22 did not show a spike in IL-10 transcription as they entered remission in contrast to controls, implying that environmentally triggered signals were blunted. Sustained activity of PTPN22, due to the gain-of-function mutation, acts as a dominant negative regulator of ERK activity leading to blunted cellular responsiveness to environmental stimuli and expression of protective cytokines.
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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.