Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis
ObjectivesThe abnormal DNA damage response is associated with upregulation of the type-1 interferon (IFN-I) pathway in certain rheumatic diseases. We investigated whether such aberrant mechanisms operate in psoriatic arthritis (PsA).MethodsDNA damage levels were measured by alkaline comet assay in p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1274060/full |
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| author | George E. Fragoulis George E. Fragoulis Panagiotis A. Ntouros Adrianos Nezos Nikolaos I. Vlachogiannis Iain B. McInnes Maria G. Tektonidou Charalampos Skarlis Vassilis L. Souliotis Vassilis L. Souliotis Clio P. Mavragani Clio P. Mavragani Petros P. Sfikakis |
| author_facet | George E. Fragoulis George E. Fragoulis Panagiotis A. Ntouros Adrianos Nezos Nikolaos I. Vlachogiannis Iain B. McInnes Maria G. Tektonidou Charalampos Skarlis Vassilis L. Souliotis Vassilis L. Souliotis Clio P. Mavragani Clio P. Mavragani Petros P. Sfikakis |
| author_sort | George E. Fragoulis |
| collection | DOAJ |
| description | ObjectivesThe abnormal DNA damage response is associated with upregulation of the type-1 interferon (IFN-I) pathway in certain rheumatic diseases. We investigated whether such aberrant mechanisms operate in psoriatic arthritis (PsA).MethodsDNA damage levels were measured by alkaline comet assay in peripheral blood mononuclear cells from 52 PsA patients and age-sex-matched healthy individuals. RNA expression of IFIT1, MX1 and IFI44, which are selectively induced by IFN-I, was quantitated by real-time polymerase chain reaction and their composite normalized expression resulted in IFN-I score calculation. RNA expression of IL1β, IL6, TNF, IL17A and IL23A was also assessed in PsA and control subgroups.ResultsIn PsA, DNA damage accumulation was increased by almost two-fold compared to healthy individuals (olive tail moment arbitrary units, mean ± SD; 9.42 ± 2.71 vs 4.88 ± 1.98, p<0.0001). DNA damage levels significantly correlated with serum C-Reactive-protein and IL6 RNA expression in PBMCs. Despite increased DNA damage, the IFN-I score was strikingly lower in PsA patients compared to controls (-0.49 ± 6.99 vs 4.24 ± 4.26; p<0.0001). No correlation was found between IFN-I pathway downregulation and DNA damage. However, the IFN-I score in a PsA subgroup was lower in those patients with higher IL1β expression, as well as in those with higher TNF/IL23A PBMCs expression.ConclusionDNA damage in PsA correlates with measures of inflammation but is not associated with the IFN-I pathway induction. The unexpected IFN-I downregulation, albeit reminiscent to findings in experimental models of spondyloarthritis, may be implicated in PsA pathogenesis and explained by operation of other cytokines. |
| first_indexed | 2024-03-09T02:37:26Z |
| format | Article |
| id | doaj.art-621e1123c1474172aaab94f3a9866808 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T02:37:26Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-621e1123c1474172aaab94f3a98668082023-12-06T08:17:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12740601274060Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritisGeorge E. Fragoulis0George E. Fragoulis1Panagiotis A. Ntouros2Adrianos Nezos3Nikolaos I. Vlachogiannis4Iain B. McInnes5Maria G. Tektonidou6Charalampos Skarlis7Vassilis L. Souliotis8Vassilis L. Souliotis9Clio P. Mavragani10Clio P. Mavragani11Petros P. Sfikakis12Joint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceDepartment of Physiology, National and Kapodistrian University of Athens Medical School, Athens, GreeceJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceDepartment of Physiology, National and Kapodistrian University of Athens Medical School, Athens, GreeceJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, Athens, GreeceJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceDepartment of Physiology, National and Kapodistrian University of Athens Medical School, Athens, GreeceJoint Academic Rheumatology Program, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, GreeceObjectivesThe abnormal DNA damage response is associated with upregulation of the type-1 interferon (IFN-I) pathway in certain rheumatic diseases. We investigated whether such aberrant mechanisms operate in psoriatic arthritis (PsA).MethodsDNA damage levels were measured by alkaline comet assay in peripheral blood mononuclear cells from 52 PsA patients and age-sex-matched healthy individuals. RNA expression of IFIT1, MX1 and IFI44, which are selectively induced by IFN-I, was quantitated by real-time polymerase chain reaction and their composite normalized expression resulted in IFN-I score calculation. RNA expression of IL1β, IL6, TNF, IL17A and IL23A was also assessed in PsA and control subgroups.ResultsIn PsA, DNA damage accumulation was increased by almost two-fold compared to healthy individuals (olive tail moment arbitrary units, mean ± SD; 9.42 ± 2.71 vs 4.88 ± 1.98, p<0.0001). DNA damage levels significantly correlated with serum C-Reactive-protein and IL6 RNA expression in PBMCs. Despite increased DNA damage, the IFN-I score was strikingly lower in PsA patients compared to controls (-0.49 ± 6.99 vs 4.24 ± 4.26; p<0.0001). No correlation was found between IFN-I pathway downregulation and DNA damage. However, the IFN-I score in a PsA subgroup was lower in those patients with higher IL1β expression, as well as in those with higher TNF/IL23A PBMCs expression.ConclusionDNA damage in PsA correlates with measures of inflammation but is not associated with the IFN-I pathway induction. The unexpected IFN-I downregulation, albeit reminiscent to findings in experimental models of spondyloarthritis, may be implicated in PsA pathogenesis and explained by operation of other cytokines.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1274060/fullpsoriatic arthritistype-I InterferonDNA damagePBMC (peripheral blood mononuclear cells)IL-6IL-1 |
| spellingShingle | George E. Fragoulis George E. Fragoulis Panagiotis A. Ntouros Adrianos Nezos Nikolaos I. Vlachogiannis Iain B. McInnes Maria G. Tektonidou Charalampos Skarlis Vassilis L. Souliotis Vassilis L. Souliotis Clio P. Mavragani Clio P. Mavragani Petros P. Sfikakis Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis Frontiers in Immunology psoriatic arthritis type-I Interferon DNA damage PBMC (peripheral blood mononuclear cells) IL-6 IL-1 |
| title | Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
| title_full | Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
| title_fullStr | Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
| title_full_unstemmed | Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
| title_short | Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
| title_sort | type i interferon pathway and dna damage accumulation in peripheral blood of patients with psoriatic arthritis |
| topic | psoriatic arthritis type-I Interferon DNA damage PBMC (peripheral blood mononuclear cells) IL-6 IL-1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1274060/full |
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