Whole blood transcriptome identifies interferon-regulated genes as key drivers in thrombotic primary antiphospholipid syndrome.

Autor: Verrou KM; Center of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Sfikakis PP; Center of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Tektonidou MG; Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: mtektonidou@gmail.com.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2023 Jan; Vol. 134, pp. 102978. Date of Electronic Publication: 2022 Dec 30.
DOI: 10.1016/j.jaut.2022.102978
Abstrakt: Objective: Pathogenesis of antiphospholipid syndrome (APS) isn't fully elucidated. We aimed to identify gene signatures characterizing thrombotic primary APS (thrPAPS) and subgroups at high risk for worse outcomes.
Methods: We performed whole blood next-generation RNA-sequencing in 62 patients with thrPAPS and 29 age-/sex-matched healthy controls (HCs), followed by differential gene expression analysis (DGEA) and enrichment analysis. We trained models on transcriptomics data using machine learning.
Results: DGEA of 12.306 genes revealed 34 deregulated genes in thrPAPS versus HCs; 33 were upregulated by at least 2-fold, and 14/33 were type I and II interferon-regulated genes (IRGs) as determined by interferome database. Machine learning applied to deregulated genes returned 79% accuracy to discriminate thrPAPS from HCs, which increased to 82% when only the most informative IRGs were analyzed. Comparison of thrPAPS subgroups versus HCs showed an increased presence of IRGs among upregulated genes in venous thrombosis (21/23, 91%), triple-antiphospholipid antibody (aPL) positive (30/50, 60%), and recurrent thrombosis (19/42, 45%) subgroups. Enrichment analysis of upregulated genes in triple-aPL positive patients revealed terms related to 'type I interferon signaling pathway' and 'innate immune response'. DGEA among thrPAPS subgroups revealed upregulated genes, including IRGs, in patients with venous versus arterial thrombosis (n = 11, 9 IRGs), triple-aPL versus non-triple aPL (n = 10, 9 IRGs), and recurrent versus non-recurrent thrombosis (n = 10, 3 IRGs).
Conclusion: Upregulated IRGs may better discriminate thrPAPS from HCs than all deregulated genes in peripheral blood. Taken together with DGEA data, IRGs are highly expressed in thrPAPS and high-risk subgroups of triple-aPL and recurrent thrombosis, with potential treatment implications.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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