Bong Jik Kim1,2, Young Ho Kim3, Seungmin Lee4, Jin Hee Han5, Sang-Yeon Lee5, Jeon Seong5, Dong-Han Lee5, Bonggi Kim1, Hye-Rim Park5, Marge Carandang6, Dooyi Oh5, Seung Ha Oh7, Joong Gon Kim3, Soyoung Lee3, Byung Yoon Choi5,8. 1. Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea, Daejeon, Korea. 2. Brain Research Institute, Chungnam National University College of Medicine, Daejeon, Korea. 3. Division of Immunology, Department of Pediatrics, Seoul National University Hospital, Seoul, Korea. 4. R&D Center, ENCell Co. Ltd, Seoul, Korea. 5. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. 6. Department of Otorhinolaryngology-Head and Neck Surgery, East Avenue Medical Center, Metro Manila, Philippines. 7. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. 8. Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea.
Abstract
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.
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 diseasecryopyrin-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.
Authors: Nadia L Samaha; Mohamad M Almasri; J Dixon Johns; Michael Hoa Journal: Curr Opin Otolaryngol Head Neck Surg Date: 2021-10-01 Impact factor: 1.814
Authors: Dominika Oziębło; Marcin L Leja; Aldona Jeznach; Magdalena Orzechowska; Tomasz Skirecki; Ewa Więsik-Szewczyk; Mariusz Furmanek; Natalia Bałdyga; Henryk Skarżyński; Monika Ołdak Journal: Front Immunol Date: 2022-05-26 Impact factor: 8.786