Sökning: onr:"swepub:oai:lup.lub.lu.se:27b44239-97c7-44cd-afda-cb505def24a4" > TET2-mutant clonal ...
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000 | 05078naa a2200553 4500 | |
001 | oai:lup.lub.lu.se:27b44239-97c7-44cd-afda-cb505def24a4 | |
003 | SwePub | |
008 | 221129s2022 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/27b44239-97c7-44cd-afda-cb505def24a42 URI |
024 | 7 | a https://doi.org/10.1182/blood.20220153842 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Agrawal, Mridulu Dana-Farber Cancer Institute4 aut |
245 | 1 0 | a TET2-mutant clonal hematopoiesis and risk of gout |
264 | 1 | b American Society of Hematology,c 2022 |
300 | a 10 s. | |
520 | a Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] ≥2%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng |
700 | 1 | a Niroula, Abhisheku Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Dana-Farber Cancer Institute4 aut0 (Swepub:lu)med-anu |
700 | 1 | a Cunin, Pierreu Boston Children's Hospital4 aut |
700 | 1 | a McConkey, Marieu Dana-Farber Cancer Institute4 aut |
700 | 1 | a Shkolnik, Veronicau Dana-Farber Cancer Institute4 aut |
700 | 1 | a Kim, Peter G.u Broad Institute,Dana-Farber Cancer Institute4 aut |
700 | 1 | a Wong, Waihay J.u Dana-Farber Cancer Institute,Broad Institute4 aut |
700 | 1 | a Weeks, Lachelle D.u Dana-Farber Cancer Institute4 aut |
700 | 1 | a Lin, Amy E.u Dana-Farber Cancer Institute,Brigham and Women's Hospital / Harvard Medical School4 aut |
700 | 1 | a Miller, Peter G.u Dana-Farber Cancer Institute,Harvard Medical School4 aut |
700 | 1 | a Gibson, Christopher J.u Dana-Farber Cancer Institute4 aut |
700 | 1 | a Sekar, Aswinu Dana-Farber Cancer Institute4 aut |
700 | 1 | a Schaefer, Inga Marieu Harvard Medical School4 aut |
700 | 1 | a Neuberg, Donnau Dana-Farber Cancer Institute4 aut |
700 | 1 | a Stone, Richard M.u Dana-Farber Cancer Institute4 aut |
700 | 1 | a Bick, Alexander G.u Vanderbilt University Medical Center4 aut |
700 | 1 | a Uddin, Md Mesbahu Broad Institute,Massachusetts General Hospital4 aut |
700 | 1 | a Griffin, Gabriel K.u Broad Institute,Harvard Medical School4 aut |
700 | 1 | a Jaiswal, Siddharthau Stanford University School of Medicine4 aut |
700 | 1 | a Natarajan, Pradeepu Broad Institute,Massachusetts General Hospital,Harvard Medical School4 aut |
700 | 1 | a Nigrovic, Peter A.u Harvard Medical School,Boston Children's Hospital4 aut |
700 | 1 | a Rao, Deepak A.u Harvard Medical School4 aut |
700 | 1 | a Ebert, Benjamin L.u Howard Hughes Medical Institute,Dana-Farber Cancer Institute4 aut |
710 | 2 | a Dana-Farber Cancer Instituteb Hematogenomics4 org |
773 | 0 | t Bloodd : American Society of Hematologyg 140:10, s. 1094-1103q 140:10<1094-1103x 0006-4971x 1528-0020 |
856 | 4 | u http://dx.doi.org/10.1182/blood.2022015384x freey FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/27b44239-97c7-44cd-afda-cb505def24a4 |
856 | 4 8 | u https://doi.org/10.1182/blood.2022015384 |
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