Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis. Issue 2 (16th September 2022)

• Record Type: Journal Article
• Authors: Atschekzei, Faranaz; Dubrowinskaja, Natalia; Anim, Manfred; Thiele, Thea; Witte, Torsten; Sogkas, Georgios
• Is Part Of: RMD open. Volume 8:Issue 2(2022)
• Publication Date: 2022-09-16
• Subjects: immune system diseases -- inflammation -- polymorphism, genetic -- epidemiology -- arthritis, psoriatic; Musculoskeletal system -- Diseases -- Periodicals; Rheumatism -- Periodicals; 616.7005
• DOI: 10.1136/rmdopen-2022-002561
• Languages: English
• ISSNs: 2056-5933

Abstract

Abstract : Objectives: Besides adaptive immunity genes, genetic risk factors for psoriatic arthritis (PsA) include innate immunity loci, which suggests an autoinflammatory disease mechanism, at least in a subset of patients. Here, we aimed at investigating the autoinflammatory genetic background of PsA. Methods: A total of 120 patients with PsA visiting the outpatient clinics of the Hannover University hospital underwent targeted next-generation sequencing, searching for variations in genes linked with inborn errors of immunity classified as autoinflammatory disorders (AIDs). Deleteriousness of rare variants was evaluated through in silico analysis. Results: We found 45 rare predicted deleterious variants in 37 out of 120 (30.8%) patients with PsA. Relatively common were variants in AP1S3, PLCG2, NOD2 and NLRP12 . All 45 variants were monoallelic and 25 of them, identified in 20 out of 120 (16.7%) patients, were localised in genes associated with autosomal dominant (AD) disorders. Detection of those variants is associated with pustular psoriasis or a coexisting inflammatory bowel disease (IBD). Conclusions: Approximately 30% of patients with PsA harboured at least one variant in a gene associated with an AID, suggesting an autoinflammatory disease mechanism. Detection of variants in genes linked to AD-AIDs may explain extra-articular manifestations of PsA, such as pustular psoriasis and IBD.