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=14

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=<sec><title>Objectives</title><p>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).</p></sec><sec><title>Methods</title><p>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 <italic>IFIT1</italic>, <italic>MX1</italic> and <italic>IFI44</italic>, 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 <italic>IL1β</italic>, <italic>IL6</italic>, <italic>TNF</italic>, <italic>IL17A</italic> and <italic>IL23A</italic> was also assessed in PsA and control subgroups.</p></sec><sec><title>Results</title><p>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 <italic>vs</italic> 4.88 ± 1.98, p&lt;0.0001). DNA damage levels significantly correlated with serum C-Reactive-protein and <italic>IL6</italic> 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 <italic>vs</italic> 4.24 ± 4.26; p&lt;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 <italic>IL1β</italic> expression, as well as in those with higher <italic>TNF</italic>/<italic>IL23A</italic> PBMCs expression.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>