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- Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With AdultāOnset Still's Disease
Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With AdultāOnset Still's Disease
Authors
Joanne Topping, Leon Chang, Fatima Nadat, James A. Poulter, Alice Ibbotson, Samuel LaraāReyna, Christopher M. Watson, Clive Carter, Linda P. Pournara, Jan Zernicke, Rebecca L. Ross, Catherine Cargo, Paul A. Lyons, Kenneth G. C. Smith, Francesco Del Galdo, JĆ¼rgen Rech, Bruno Fautrel, Eugen Feist, Michael F. McDermott, Sinisa Savic,
Abstract
Objective
Adultāonset Still disease (AOSD) is a systemic autoinflammatory disorder (AID) of unknown etiology. Genetic studies have been limited. Here, we conducted detailed genetic and inflammatory biomarker analysis of a large cohort with AOSD to investigate the underlying pathology and identify novel targets for potential treatment.
Methods
We investigated AOSD cases (n = 60) for rare germline and somatic variants using whole exome sequencing with virtual gene panels. Transcriptome profiles were investigated by bulk RNA sequencing whole blood. Cytokine profiling was performed on an extended patient cohort (n = 106) alongside measurements of
Results
We observed higher than expected frequencies of rare germline variants associated with monogenic AIDs in AOSD cases (AOSD 38.4% vs healthy controls [HCs] 20.4%) and earlier onset of putative somatic variants associated with clonal hematopoiesis of indeterminate potential. Transcriptome profiling revealed a positive correlation between Still Activity Score and gene expression associated with the innate immune system. ASC/
Conclusion
Our study shows considerable genetic complexity within AOSD and demonstrates the potential utility of the ASC/
Members
FANNY COFFIN
IngƩnieur de recherche Inserm
JULIEN ROMEJON
IngƩnieur de recherche
HENRI DE SOYRES
IngƩnieur d'Ʃtudes
APOLLINE GALLOIS
IngƩnieur de recherche