Otological aspects of NLRP3-related autoinflammatory disorder focusing on the responsiveness to anakinra

Bong Jik Kim, Young Ho Kim, Seungmin Lee, Jin Hee Han, Sang Yeon Lee, Jeon Seong, Dong Han Lee, Bonggi Kim, Hye Rim Park, Marge Carandang, Dooyi Oh, Seung Ha Oh, Joong Gon Kim, Soyoung Lee, Byung Yoon Choi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Objectives: Gradually progressive sensorineural hearing loss (SNHL) is a prevalent sensory defect. It is generally untreatable, making rehabilitation by hearing aid or cochlear implantation the only option. However, SNHL as one of the symptoms of the hereditary autoinflammatory systemic disease cryopyrin-associated periodic syndrome, or as the only symptom of the cochlea-specific form (DFNA34), was suggested to respond to IL-1 antagonist (anakinra) therapy, which ameliorates NLRP3 variants-induced over-secretion of IL-1β. We analysed genotypic and phenotypic spectrum of cryopyrin-associated periodic syndrome or DFNA34, specifically focusing on the responsiveness of SNHL to anakinra. Methods: Seventeen families diagnosed with either cryopyrin-associated periodic syndrome or DFNA34 were recruited. Genotyping and phenotyping including audiogram, MRI findings, and in vitro IL-1β assay were performed. Results: Our cohort had an etiologic homogeneity of 94.1% to NLRP3 variants and a high de novo occurrence (84.6%). We identified the second DNFA34 pedigree worldwide with a novel NLRP3 variant supported by in vitro analysis. Significant improvement of hearing status against the natural course, showing response to anakinra, was identified in three probands, one of whom used to have severe SNHL. Hearing threshold worse than 60 dB at the start of anakinra and cochlear enhancement on brain MRI seemed to be related with poor audiologic prognosis and responsiveness to anakinra therapy despite stabilized systemic symptoms and inflammatory markers. Conclusion: We propose a constellation of biomarkers comprising NLRP3 genotypes, hearing status at diagnosis, and cochlear radiological findings as prognostic factors of hearing status after anakinra treatment and possibly as sensitive parameters for treatment dosage adjustment.

Original languageEnglish
Pages (from-to)1523-1532
Number of pages10
JournalRheumatology (United Kingdom)
Issue number3
StatePublished - 1 Mar 2021


  • NLRP3
  • anakinra
  • autoinflammatory
  • cryopyrin-associated periodic syndrome
  • sensorineural hearing loss


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