{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:07:16Z","timestamp":1790312836457,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ek0109478"],"award-info":[{"award-number":["21ek0109478"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22H03041"],"award-info":[{"award-number":["22H03041"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22KK0113"],"award-info":[{"award-number":["22KK0113"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23ek0109623"],"award-info":[{"award-number":["JP23ek0109623"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek019754"],"award-info":[{"award-number":["JP24ek019754"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Objective<\/jats:title>\n \n Cryopyrin\u2010associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain\u2010of\u2010function mutations in\n NLRP3<\/jats:italic>\n . Although somatic\n NLRP3<\/jats:italic>\n mosaicism is increasingly recognized, it remains unclear how variant allele frequency (VAF) changes over time and whether age at disease onset reflects differences in somatic mutation dynamics. This study aimed to analyze the longitudinal VAF trends and their correlation with clonal hematopoiesis (CH) in patients with CAPS mosaicism.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analyzed\n NLRP3<\/jats:italic>\n VAF in blood and various tissues, including dried umbilical cord (DUC), using digital polymerase chain reaction and deep amplicon sequencing. Whole\u2010exome and single\u2010cell genome sequencing were performed to evaluate CH\u2010related mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We included 15 patients with VAFs of 4.3% to 34.9%. In the 12 early\u2010onset cases, VAFs were generally consistent across various tissues and did not increase over time, including the DUC. Conversely, in the three late\u2010onset cases, VAFs were particularly high in myeloid cells. Notably, in one late\u2010onset case, no mutations were detected in DUC. After disease onset, VAFs exhibited a 2.9% to 10.6% and a 6.2% to 16.4% increase in the whole blood and neutrophils over 6.4 and 4.4 years, respectively, showing a clonal expansion of\n NLRP3<\/jats:italic>\n mutant cells. Single\u2010cell genome sequencing revealed frequent co\u2010occurrence of\n NLRP3<\/jats:italic>\n and\n TET2<\/jats:italic>\n mutations in the same cells, with a gradual increase in both VAFs over three years in one late\u2010onset case.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In early\u2010onset cases, the VAFs were comparable across various tissues and did not increase over time. Mutations in late\u2010onset cases were enriched in myeloid cells, and VAFs were increased, suggesting a link to CH.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.43329","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T09:20:28Z","timestamp":1753176028000},"page":"231-242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Longitudinal Analysis of Somatic Mosaicism and Clonal Hematopoiesis in Cryopyrin\u2010Associated Periodic Syndrome"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5104-9851","authenticated-orcid":false,"given":"Kentaro","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Pediatrics Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-0648","authenticated-orcid":false,"given":"Yoshitaka","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medicine, Institute for the Advanced Study of Human Biology, and Department of Immunology, Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kamatani","sequence":"additional","affiliation":[{"name":"Department of AI Technology Development, M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo and Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment Institute of Science Tokyo Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Murakami","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-7772","authenticated-orcid":false,"given":"Masaki","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Neonatal and Maternal Medicine, Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Komai","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology Graduate School of Medicine, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology and Immune\u2010Mediated Diseases Therapy Center Graduate School of Medicine, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Yasumura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences and Department of Pediatrics Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Rheumatology Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-1494","authenticated-orcid":false,"given":"Yuichi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kagoshima University Hospital Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syuji","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kagoshima University Hospital Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Graduate School of Medicine Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyo","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dokkyo Medical University Saitama Medical Center Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinao","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Immunology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Umebayashi","sequence":"additional","affiliation":[{"name":"Department of Rheumatism, Infection Disease Miyagi Children's Hospital Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Nishimata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Rheumatology Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Applied Genomics Kazusa DNA Research Institute Kisarazu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-4952","authenticated-orcid":false,"given":"Naotomo","family":"Kambe","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medicine, Kyoto University and Center for Allergy, Kyoto University Hospital Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kitamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utako","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Mie University Graduate School of Medicine and Center for Rheumatic Diseases, Mie University Hospital Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tokushima Red Cross Hospital Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nihira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan, and Department of Pediatrics Kyoto Okamoto Memorial Hospital Kuse Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan, and Department of Pediatrics Otsu Red Cross Hospital Otsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitaro","family":"Hiejima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-5254","authenticated-orcid":false,"given":"Keishi","family":"Fujio","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology Graduate School of Medicine, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Mie University Graduate School of Medicine and Center for Rheumatic Diseases, Mie University Hospital Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Live Cell Diagnosis, Ltd Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Shirasaki","sequence":"additional","affiliation":[{"name":"Research Center for Advanced Science and Technology The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumu K.","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Clinical Application Center for iPS Cell Research and Application, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hiroshima University Graduate School of Biomedical and Health Sciences Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Institute for the Advanced Study of Human Biology and Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Takita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ohara","sequence":"additional","affiliation":[{"name":"Department of Applied Genomics Kazusa DNA Research Institute Kisarazu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-6158","authenticated-orcid":false,"given":"Ryuta","family":"Nishikomori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kurume University Graduate School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yasumi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Japan Environment and Children's Study Kyoto Regional Centre Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-0936","authenticated-orcid":false,"given":"Kazushi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kyoto University Graduate School of Medicine and Center for Allergy, Kyoto University Hospital Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxz047"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00638-z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.08.017"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21404"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30512"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204361"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.035"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39770"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01410"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39190"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.06.153"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2212928"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42808"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3066"},{"key":"e_1_2_7_17_1","article-title":"Isolation of human neutrophils from whole blood and buffy coats","volume":"175","author":"Hsu AY","year":"2021","journal-title":"J Vis Exp"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2819-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-022-06130-1"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/mrcr\/rxad067"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39960"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5243.1744-b"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094201"},{"issue":"3","key":"e_1_2_7_24_1","first-page":"244","article-title":"Spectrum of clonal hematopoiesis in VEXAS syndrome","volume":"142","author":"Gutierrez\u2010Rodrigues F","year":"2023","journal-title":"Blood"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0247-5"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00710-0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43697-y"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016835"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.032"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02088-9"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-14-105"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.157"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.14583"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.43329","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.43329","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.43329","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:30:11Z","timestamp":1769689811000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.43329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/art.43329"],"URL":"https:\/\/doi.org\/10.1002\/art.43329","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]},"assertion":[{"value":"2025-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}