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 6 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
2 · The registry
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.
3 · Its place in the literature
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
35 authors at 8 institutions in 3 countries.
Yaoyuan ZhangDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-0256-098X
Rhiannon Morris *Walter and Eliza Hall Institute of Medical Research , Parkville, Australia.ORCID 0000-0001-6817-6609
Grant J Brown *Division of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-9721-5539
Ayla May D LorenzoDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0009-0002-4834-9618
Xiangpeng MengDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0003-3447-0871
Nadia J KershawWalter and Eliza Hall Institute of Medical Research , Parkville, Australia.ORCID 0000-0002-3554-2622
Pamudika KiridenaDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-5350-3360
Gaétan BurgioDivision of Genome Sciences and Cancer, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-7434-926X
Simon GrossDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0009-0007-0735-9621
Jean Y CappelloDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0003-0114-7912
Qian ShenDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.
Hao WangDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0001-8228-5633
Cynthia TurnbullDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-9976-4005
Tom Lea-HenryDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-0447-7944
Maurice StanleyDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-1445-0892
Zhijia YuDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-4763-4698
Fiona D BallardDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-0707-9706
Aaron ChuahDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0003-3066-701X
Ann-Maree HatchDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0009-0001-1916-8175
Anselm EndersDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0001-5933-6463
Seth L MastersWalter and Eliza Hall Institute of Medical Research , Parkville, Australia.ORCID 0000-0003-4763-576X
Alexander P HeadleyConcord Repatriation General Hospital , Concord, Australia.ORCID 0009-0004-0763-2729
Mario ŠestanDepartment of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.ORCID 0000-0003-1092-6491
Marija JelušićDepartment of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.ORCID 0000-0002-1728-4260
Matthew C CookDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-3331-9363
Vicki AthanasopoulosDivision of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0002-5764-5948
David A FulcherCentre for Personalised Immunology, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0001-9270-2269
Jeffrey J BabonWalter and Eliza Hall Institute of Medical Research , Parkville, Australia.ORCID 0000-0002-5408-6239
Carola G Vinuesa *Division of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0001-9799-0298
Julia I Ellyard *Division of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Acton, Australia.ORCID 0000-0001-6301-2533
Australian National University · AUThe University of Melbourne · AUCanberra Hospital · AUUniversity Hospital Centre Zagreb · HRChildren's Health Queensland Hospital and Health Service · AUConcord Repatriation General Hospital · AUFiona Stanley Hospital · AUThe Francis Crick Institute · GB
Funding
Australian GovernmentNational Collaborative Research Infrastructure StrategyNational Computational InfrastructureNational Health and Medical Research CouncilWellcome Trust CC2228
6 · The paper itself
Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair the negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role for SH2B3 in human B cell tolerance and lupus risk.
Indexed as
AutoimmunityLupus Erythematosus, SystemicAdaptor Proteins, Signal TransducingAnimalsB-Cell Activating FactorB-LymphocytesHumansMicePrecursor Cells, B-LymphoidAdaptor Proteins, Signal TransducingB-Cell Activating FactorSH2B3 protein, human
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.
Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity. · full record | OpenQuestion