ArticleThe Journal of experimental medicine2024
Haploinsufficiency in PTPN2 leads to early-onset systemic autoimmunity from Evans syndrome to lupus.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Ptpn2 limits plasma cell fate and antiviral immunity by integrating B cell receptor and IFN-γ signals in B cells.Science advances · 2026Article
- Molecular Mechanisms and Targeted Therapies of PTPN2 in Metabolic Diseases: A Review.Biomolecules · 2026Review
- A novel linker region truncating variant in BCL10 underlies a leaky immunodeficiency phenotype.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Exome sequencing enables molecular diagnosis in 10% of early-onset or familial systemic lupus erythematosus cases.EBioMedicine · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Insights into the pathogenesis of childhood-onset SLE in the past decade.Nature reviews. Rheumatology · 2026Review
- Deletion of Ptpn2 in B cells promotes autoimmunity via TLR and JAK/STAT signaling.JCI insight · 2025Article
- Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.Current rheumatology reports · 2025Review
- In silico modeling guides identification of novel JAK1 variants associated with immune dysregulation.EMBO molecular medicine · 2025Article
- Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition.iScience · 2025Article
- Rheumatologic and Autoimmune Features of Inborn Errors of Immunity: Implications for Diagnosis and Management.Journal of human immunity · 2025Article
- STAT3 haploinsufficiency is associated with autosomal dominant hyper-IgE syndrome.Science advances · 2025Article
- Insights from the 2024 pediatric rheumatology basic/translational years in review.Pediatric rheumatology online journal · 2025Review
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.Current opinion in rheumatology · 2025Review
- Autoinflammatory encephalopathy due to PTPN1 haploinsufficiency: a case series.The Lancet. Neurology · 2025Article
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions.Frontiers in immunology · 2025Review
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24 authors.
Funding
Abstract
An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells. Furthermore, patients exhibited high serum levels of inflammatory cytokines, mimicking the profile observed in individuals with gain-of-function mutations in STAT factors. Flow cytometry analysis of patients' blood cells revealed typical alterations associated with autoimmunity and all patients presented with autoantibodies. These findings further supported the notion that a loss of function in negative regulators of cytokine pathways can lead to a broad spectrum of autoimmune manifestations and that PTPN2 along with SOCS1 haploinsufficiency constitute a new group of monogenic autoimmune diseases that can benefit from targeted therapy.
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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 Socratic graph.