ArticleJCI insight2016
A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- The effect of tumor necrosis factor-alpha on rheumatoid arthritis-related pain: overview of evidence and mechanistic pathways.Croatian medical journal · 2026Review
- Regulation of basal and tumour necrosis factor α-induced fibroblast gene expression by peptidylarginine deiminase 2.The Journal of physiology · 2026Article
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation.Science translational medicine · 2025Article
- Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.The Journal of clinical investigation · 2025Article
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
- Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.bioRxiv : the preprint server for biology · 2024Article
- Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.Nature reviews. Rheumatology · 2024Review
- Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease.Cellular & molecular immunology · 2024Article
- The Role of Citrullination Modification in CD4Biomolecules · 2024Review
- The association of common autoimmune diseases with autoimmune thyroiditis: a two-sample Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice.The Journal of clinical investigation · 2023Article
- Anti-citrullinated α-enolase peptide as a highly sensitive autoantigen in patients with rheumatoid arthritis.Heliyon · 2023Article
- Microbiota-dependent indole production is required for the development of collagen-induced arthritis.bioRxiv : the preprint server for biology · 2023Article
- Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA.Frontiers in immunology · 2023Article
- Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain ofScience translational medicine · 2022Article
- Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study.RMD open · 2022Article
- Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications.Nature reviews. Rheumatology · 2022Review
- RNA Editing-Associated Post-Transcriptional Gene Regulation in Rheumatoid Arthritis.Bioinformatics and biology insights · 2022Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
A unique feature of rheumatoid arthritis (RA) is the presence of anti-citrullinated protein antibodies (ACPA). Several risk factors for RA are known to increase the expression or activity of peptidyl arginine deiminases (PADs), which catalyze citrullination and, when dysregulated, can result in hypercitrullination. However, the consequence of hypercitrullination is unknown and the function of each PAD has yet to be defined. Th cells of RA patients are hypoglycolytic and hyperproliferative due to impaired expression of PFKFB3 and ATM, respectively. Here, we report that these features are also observed in peripheral blood mononuclear cells (PBMCs) from healthy at-risk individuals (ARIs). PBMCs of ARIs are also hypercitrullinated and produce more IL-2 and Th17 cytokines but fewer Th2 cytokines. These abnormal features are due to impaired induction of PTPN22, a phosphatase that also suppresses citrullination independently of its phosphatase activity. Attenuated phosphatase activity of PTPN22 results in aberrant expression of IL-2, ATM, and PFKFB3, whereas diminished nonphosphatase activity of PTPN22 leads to hypercitrullination mediated by PADs. PAD2- or PAD4-mediated hypercitrullination reduces the expression of Th2 cytokines. By contrast, only PAD2-mediated hypercitrullination can increase the expression of Th17 cytokines. Taken together, our data depict a molecular signature of preclinical RA that is triggered by impaired induction of PTPN22.
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