BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1652177
Adult onset cryopyrin-associated periodic syndrome due to germline missense mutation in NLRP3 in a previously healthy middle-aged woman
Provisionally accepted
- 1Seoul National University Hospital, Seoul, Republic of Korea
- 2Seoul National University Hospital, Jongno-gu, Republic of Korea
- 3Chung-Ang University Gwangmyeong Hospital, Gwangmyeong-si, Republic of Korea
- 4Seoul National University College of Medicine, Jongno-gu, Republic of Korea
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Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by a gain-of-function mutation in the NLRP3 gene, which regulates inflammasome-mediated interleukin (IL)-1β production. This leads to recurrent episodes of fever, rash, and arthritis, typically beginning in childhood.Objective: To demonstrate the role of a missense mutation c.386A>G in NLRP3 in adult-onset CAPS in a previously healthy middle-aged woman.Whole-exome sequencing was performed. Serum levels of IL-1β, IL-1 receptor antagonist (IL-1RA), and tumor necrosis factor (TNF)-α 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.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 NLRP3 gene (NM_001243133, c.386A>G, p.Lys129Arg). Serum IL-1RA levels were significantly elevated during active disease.Monocytes from the patient produced high levels of IL-1β and TNF-α upon LPS stimulation.Treatment with anakinra ameliorated all symptoms and normalized inflammatory cytokine overproduction in the monocytes.We report a case of adult-onset CAPS in a previously healthy woman, caused by a missense mutation (c.386A>G) in the NLRP3 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.
Keywords: Autoinflamatory diseases, Cryopyrin associated periodic syndrome (CAPS), anakinra, adult onset, Mutation, IL-1
Received: 23 Jun 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Cho, Kim, Kim, Kim, Pyeon, Lee and Park. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jin Kyun Park, Seoul National University Hospital, Jongno-gu, Republic of Korea
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