Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis

Fragoulis, G. E., Ntouros, P. A., Nezos, A., Vlachogiannis, N. I., McInnes, I. B. , Tektonidou, M. G., Skarlis, C., Souliotis, V. L., Mavragani, C. P. and Sfikakis, P. P. (2023) Type-I interferon pathway and DNA damage accumulation in peripheral blood of patients with psoriatic arthritis. Frontiers in Immunology, 14, 1274060. (doi: 10.3389/fimmu.2023.1274060) (PMID:38124740) (PMCID:PMC10731026)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Fragoulis, Dr George

Creator Roles

Fragoulis, G.: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review and editing
McInnes, I.: Investigation, Writing – review and editing

• Authors: Fragoulis, G. E., Ntouros, P. A., Nezos, A., Vlachogiannis, N. I., McInnes, I. B., Tektonidou, M. G., Skarlis, C., Souliotis, V. L., Mavragani, C. P., and Sfikakis, P. P.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Frontiers in Immunology
• Publisher: Frontiers Media S.A.
• ISSN: 1664-3224
• ISSN (Online): 1664-3224
• Copyright Holders: Copyright © 2023 Fragoulis, Ntouros, Nezos, Vlachogiannis, McInnes, Tektonidou, Skarlis, Souliotis, Mavragani and Sfikakis.T
• First Published: First published in Frontiers of Immunology 14:1274060
• Publisher Policy: Reproduced under a creative commons licence