Clinical presentation and genetic variants in patients with autoinflammatory diseases

• Verfasst von: Blank, Norbert [VerfasserIn]
• Verfasst von: Kötter, Ina [VerfasserIn]
• Verfasst von: Schmalzing, Marc [VerfasserIn]
• Verfasst von: Rech, Jürgen [VerfasserIn]
• Verfasst von: Krause, Karoline [VerfasserIn]
• Verfasst von: Köhler, Birgit [VerfasserIn]
• Verfasst von: Kaudewitz, Dorothee [VerfasserIn]
• Verfasst von: Nitschke, Martin [VerfasserIn]
• Verfasst von: Haas, Christian S. [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Krusche, Martin [VerfasserIn]
• Titel: Clinical presentation and genetic variants in patients with autoinflammatory diseases
• Titelzusatz: results from the German GARROD registry
• Verf.angabe: Norbert Blank, Ina Kötter, Marc Schmalzing, Jürgen Rech, Karoline Krause, Birgit Köhler, Dorothee Kaudewitz, Martin Nitschke, Christian S. Haas, Hanns-Martin Lorenz, Martin Krusche
• Jahr: 2023
• Umfang: 9 S.
• Fussnoten: Online veröffentlicht: 25. September 2023 ; Gesehen am 14.11.2023
• Titel Quelle: Enthalten in: Rheumatology international
• Ort Quelle: Berlin : Springer, 1981
• Jahr Quelle: 2023
• Band/Heft Quelle: (2023), Seite 1-9
• ISSN Quelle: 1437-160X
• DOI: doi:10.1007/s00296-023-05443-x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Anakinra
• Sach-SW: Canakinumab
• Sach-SW: Cryopyrin-associated periodic syndrome
• Sach-SW: Familial Mediterranean fever
• Sach-SW: Mevalonate kinase deficiency
• Sach-SW: Tumor necrosis factor receptor-associated periodic syndrome
• K10plus-PPN: 187022941X

Abstract

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.