Type-I Interferon Pathway and DNA Damage Accumulation in Peripheral Blood of Patients with Psoriatic Arthritis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Dec 21

PMID 38124740

Authors

George E Fragoulis

Panagiotis A Ntouros

Adrianos Nezos

Nikolaos I Vlachogiannis

Iain B McInnes

Maria G Tektonidou

Charalampos Skarlis

Vassilis L Souliotis

Clio P Mavragani

Petros P Sfikakis

Affiliations

Soon will be listed here.

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 , and , 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 , , , and 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 4.88 ± 1.98, p<0.0001). DNA damage levels significantly correlated with serum C-Reactive-protein and 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 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 expression, as well as in those with higher / 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.

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