Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis
Copyright © 2023 Fragoulis, Ntouros, Nezos, Vlachogiannis, McInnes, Tektonidou, Skarlis, Souliotis, Mavragani and Sfikakis..
Objectives: The 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).
Methods: DNA 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.
Results: In 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.
Conclusion: DNA 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 14., Seite 1274060 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fragoulis, George E [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 22.12.2023 Date Revised 25.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1274060 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366153986 |
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| 100 | 1 | |a Fragoulis, George E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis |
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| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Fragoulis, Ntouros, Nezos, Vlachogiannis, McInnes, Tektonidou, Skarlis, Souliotis, Mavragani and Sfikakis. | ||
| 520 | |a Objectives: The 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) | ||
| 520 | |a Methods: DNA 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 | ||
| 520 | |a Results: In 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 | ||
| 520 | |a Conclusion: DNA 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNA damage | |
| 650 | 4 | |a IL-1 | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a PBMC (peripheral blood mononuclear cells) | |
| 650 | 4 | |a psoriatic arthritis | |
| 650 | 4 | |a type-I Interferon | |
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| 700 | 1 | |a Ntouros, Panagiotis A |e verfasserin |4 aut | |
| 700 | 1 | |a Nezos, Adrianos |e verfasserin |4 aut | |
| 700 | 1 | |a Vlachogiannis, Nikolaos I |e verfasserin |4 aut | |
| 700 | 1 | |a McInnes, Iain B |e verfasserin |4 aut | |
| 700 | 1 | |a Tektonidou, Maria G |e verfasserin |4 aut | |
| 700 | 1 | |a Skarlis, Charalampos |e verfasserin |4 aut | |
| 700 | 1 | |a Souliotis, Vassilis L |e verfasserin |4 aut | |
| 700 | 1 | |a Mavragani, Clio P |e verfasserin |4 aut | |
| 700 | 1 | |a Sfikakis, Petros P |e verfasserin |4 aut | |
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