{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:33:02Z","timestamp":1793291582204,"version":"4.5.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR070765"],"award-info":[{"award-number":["RS-2022-NR070765"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by a gain-of-function mutation in the <jats:italic>NLRP3<\/jats:italic> gene, which regulates inflammasome-mediated interleukin-1\u03b2 (IL-1\u03b2) production. This leads to recurrent episodes of fever, rash, and arthritis, typically beginning in childhood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To demonstrate the role of a missense mutation, c.386A&amp;gt;G, in <jats:italic>NLRP3<\/jats:italic> in adult-onset CAPS in a previously healthy middle-aged woman.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole-exome sequencing was performed. Serum levels of IL-1\u03b2, interleukin-1 receptor antagonist (IL-1RA), and tumor necrosis factor \u03b1 (TNF-\u03b1) were measured. CD14-positive monocytes, isolated from the patient before and during IL-1 inhibition therapy, were stimulated with lipopolysaccharide (LPS), and cytokine production was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 47-year-old woman presented with recurrent periorbital swelling and inflammatory symptoms, along with elevated IL-1RA and IL-6 levels. Genetic analysis revealed a heterozygous missense mutation in the <jats:italic>NLRP3<\/jats:italic> gene (NM_001243133, c.386A&amp;gt;G, p.Lys129Arg). Serum IL-1RA levels were significantly elevated during active disease. Monocytes from the patient produced high levels of IL-1\u03b2 and TNF-\u03b1 upon LPS stimulation. Treatment with anakinra ameliorated all symptoms and normalized inflammatory cytokine overproduction in the monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a case of adult-onset CAPS in a previously healthy woman, caused by a missense mutation (c.386A&amp;gt;G) in the <jats:italic>NLRP3<\/jats:italic> gene, who exhibited a remarkable response to anakinra treatment. Autoinflammatory diseases should be considered in patients presenting with fever, skin rashes, and systemic symptoms, regardless of age.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1652177","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:26:56Z","timestamp":1756099616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Adult onset cryopyrin-associated periodic syndrome due to germline missense mutation in NLRP3 in a previously healthy middle-aged woman"],"prefix":"10.3389","volume":"16","author":[{"given":"Sung Ik","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheehyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju 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