Session Information
Session Type: Poster Session C
Session Time: 10:30AM-12:30PM
Background/Purpose: Loss of negative regulator in ISG15 and USP18 results in recently described immunodysregulatory disorders with diversity of clinical characteristics related to enhanced IFN-a/b immunity. We aim to describe the phenotype, genotype and outcome of Saudi children with proved pathogenic mutation of ISG15/USP18 genes.
Methods: Multicenter descriptive study of pediatric patients with final genetically confirmed type I interferonopathies and ISG15/USP18 gene mutation. Medical records were reviewed for demographic, clinical and genetic data.
Results: Total of fourteen patients from unrelated six Saudi families; only nine had proven gene mutation. Five patients (55%) presented within the first two years. Median age of disease onset was twenty-four months. Constitutional features were found in all patients. The most frequent organ involvements were neurology (77%), pulmonary (66%), skin abscess (55%), and musculoskeletal (44%). All patients had elevated inflammatory markers. Two patients had severe macrophage activation syndrome. Autoantibodies were evident in five patients; two of them developed lupus like disease. Four patients had abnormal immunology work up and three had recurrent infections. Genetic sequencing identified ISG15 gene mutation in eight patients, of which all had novel genetic variants. Only one patient had USP18 gene mutation with previously reported variant. Majority of the patients were treated with corticosteroids (n=8), immunoglobulin (n=3), Janus kinase inhibitors (n=2), in addition to various other immunosuppressive agents. Only one patient died with multiorgan failure.
Conclusion: Loss of negative regulator in ISG15 and USP18 genes highlight a recently described interferon mediated disease. This the first and largest cohort from the Arab region to date. In this report we expand the clinical and genetic spectrum with novel identified variants of this seldom reported disease entity along with diversity of disease severity and outcome.
To cite this abstract in AMA style:
Alsaleem A, Abdulghaffar W, Akbar L, Alhassan M, Alkhars F, Al-Mayouf S. Evolving Phenotypic and Genotypic Spectrum of Human ISG15 and USP18 Deficiencies [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/evolving-phenotypic-and-genotypic-spectrum-of-human-isg15-and-usp18-deficiencies/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/evolving-phenotypic-and-genotypic-spectrum-of-human-isg15-and-usp18-deficiencies/