- Accueil >
- Publications >
- Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With Adult‐Onset Still's Disease
Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With Adult‐Onset Still's Disease
Auteurs
Joanne Topping, Leon Chang, Fatima Nadat, James A. Poulter, Alice Ibbotson, Samuel Lara‐Reyna, 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, Jürgen Rech, Bruno Fautrel, Eugen Feist, Michael F. McDermott, Sinisa Savic,
Résumé
Objective
Adult‐onset 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/
Membres
FANNY COFFIN
Ingénieur de recherche Inserm
JULIEN ROMEJON
Ingénieur de recherche
HENRI DE SOYRES
Ingénieur d'études
APOLLINE GALLOIS
Ingénieur de recherche