AUTHOR=Fragoulis George E. , Ntouros Panagiotis A. , Nezos Adrianos , Vlachogiannis Nikolaos I. , McInnes Iain B. , Tektonidou Maria G. , Skarlis Charalampos , Souliotis Vassilis L. , Mavragani Clio P. , Sfikakis Petros P. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1274060

DOI=10.3389/fimmu.2023.1274060

ISSN=1664-3224

ABSTRACT=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).: 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, IL17Α and IL23Α 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.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.