Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-09-01
|
| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/8/2/e002561.full |
| _version_ | 1797996283174060032 |
|---|---|
| author | Torsten Witte Georgios Sogkas Natalia Dubrowinskaja Manfred Anim Faranaz Atschekzei Thea Thiele |
| author_facet | Torsten Witte Georgios Sogkas Natalia Dubrowinskaja Manfred Anim Faranaz Atschekzei Thea Thiele |
| author_sort | Torsten Witte |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T10:15:04Z |
| format | Article |
| id | doaj.art-63c09c2e144f47d190d3b241fcac884d |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-04-11T10:15:04Z |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj.art-63c09c2e144f47d190d3b241fcac884d2022-12-22T04:29:59ZengBMJ Publishing GroupRMD Open2056-59332022-09-018210.1136/rmdopen-2022-002561Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritisTorsten Witte0Georgios Sogkas1Natalia Dubrowinskaja2Manfred Anim3Faranaz Atschekzei4Thea Thiele51 Rheumatology and Immunology, Hannover Medical School, Hannover, Germany1 Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyRheumatology and Immunology, Hannover Medical University, Hannover, GermanyRheumatology and Immunology, Hannover Medical University, Hannover, Germany1 Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyObjectives 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.https://rmdopen.bmj.com/content/8/2/e002561.full |
| spellingShingle | Torsten Witte Georgios Sogkas Natalia Dubrowinskaja Manfred Anim Faranaz Atschekzei Thea Thiele Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis RMD Open |
| title | Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| title_full | Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| title_fullStr | Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| title_full_unstemmed | Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| title_short | Identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| title_sort | identification of variants in genes associated with autoinflammatory disorders in a cohort of patients with psoriatic arthritis |
| url | https://rmdopen.bmj.com/content/8/2/e002561.full |
| work_keys_str_mv | AT torstenwitte identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis AT georgiossogkas identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis AT nataliadubrowinskaja identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis AT manfredanim identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis AT faranazatschekzei identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis AT theathiele identificationofvariantsingenesassociatedwithautoinflammatorydisordersinacohortofpatientswithpsoriaticarthritis |