{ "abstract": "Background\n\nThe type I interferon-alpha (IFN-α) gene expression signature refers to the analysis of specific IFN-stimulated genes (ISG) as a surrogate measure of IFN-α pathway activity. It is widely used to assess IFN-α activity in patients with systemic lupus erythematosus (SLE), as well as to evaluate treatment response or serve as an index of disease activity. ISGs are often aggregated into a composite score that provides a quantitative measure. However, previous literature has employed differing combinations of ISG, and no clear consensus exists regarding which should be preferentially used. Our study aims to identify the combination of IGS that best correlates with serum IFN-α levels in patients with SLE.Methods\n\nA total of 252 patients with SLE were recruited in this cross-sectional study. IFN-α serum levels were measured using Simoa (Single Molecule Array) technique. Based on prior literature, 72 transcripts previously used in other studies in rheumatic musculoskeletal diseases were selected and analyzed by qPCR using Nanostring® technology. Fifty-one distinct IFN scores were computed using previously reported ISG combinations. Besides, LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis was performed to identify the minimal and most parsimonious combination of ISGs associated with serum IFN-α levels.Results\n\nLASSO analysis identified a 13-ISG combination as the most parsimonious predictor of serum IFN-α levels. However, the IFN score constructed using these 13 genes showed lower correlation with serum IFN-α levels than previously reported IFN scores from the literature. This suggests that statistically derived ISG selection is inferior to mechanistically- or pathophysiologically-informed gene combinations. Three literature-derived ISG combinations-IFI44L IFIT1 RSAD2 IFI27 ISG15 SIGLEC1, IFI27 IFI44 IFI44L RSAD2, and IFI44L IFI44 RSAD2 IFI27 IFI6-demonstrated high IFN-α correlations, statistically indistinguishable from each other but significantly superior to the remaining 48 combinations.Conclusions\n\nThis study provides evidence-based recommendations for ISG selection in constructing optimal IFN signatures to accurately predict serum IFN-α levels in SLE patients.", "abstract_shown": true, "affiliations": [ "Division of Central Laboratory, Hospital Universitario de Canarias, Tenerife, Spain.", "Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.", "Division of Rheumatology, Hospital Insular, Las Palmas de Gran Canaria, Spain.", "Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain.", "Department of Immunology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.", "Department of Medical and Surgical Sciences, CIBER Epidemiología y Salud Pública (CIBERESP), University of Cantabria, Santander, Spain.", "Division of Rheumatology, IIS-Fundación Jiménez Díaz, Madrid, Spain.", "Division of Rheumatology, IIS-Fundación Jiménez Díaz, Madrid, Spain. miguelaggay@hotmail.com.", "Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain. miguelaggay@hotmail.com.", "Instituto de Investigaciones Sanitarias de Canarias (IISC), Tenerife, Spain. iferraza@ull.edu.es.", "Department of Internal Medicine, University of La Laguna (ULL), Tenerife, Spain. iferraza@ull.edu.es.", "Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Santander, Tenerife, Spain. iferraza@ull.edu.es." ], "article_type": "research article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0 ], "name": "Marta Rodríguez-García", "orcid": "0009-0008-6628-0371" }, { "affs": [ 0 ], "name": "Fuensanta Gómez-Bernal", "orcid": "0000-0002-8597-1943" }, { "affs": [ 1 ], "name": "Juan Carlos Quevedo-Abeledo", "orcid": "0000-0003-0398-9072" }, { "affs": [ 2 ], "name": "Beatriz Tejera-Segura", "orcid": "0000-0001-5124-8944" }, { "affs": [ 3 ], "name": "Enrique García-Barrera" }, { "affs": [ 3 ], "name": "Luisa María Villar", "orcid": "0000-0002-9067-3668" }, { "affs": [ 4 ], "name": "Javier Gonzalo Ocejo-Vinyals", "orcid": "0000-0003-2245-4639" }, { "affs": [ 4 ], "name": "Nerea Mota-Pérez" }, { "affs": [ 5 ], "name": "Javier Llorca", "orcid": "0000-0001-8569-861X" }, { "affs": [ 6 ], "name": "Raquel Largo", "orcid": "0000-0001-6525-2944" }, { "affs": [ 7, 8 ], "name": "Miguel Ángel González-Gay", "orcid": "0000-0002-7924-7406" }, { "affs": [ 9, 10, 11 ], "name": "Iván Ferraz-Amaro", "orcid": "0000-0003-0197-5267" } ], "bibtex": "https://research.draconitic.com/paper/4f037bs7zxtbg.bib", "cited_by": 0, "doi": "10.1186/s12916-026-05102-5", "fulltext_url": "https://europepmc.org/articles/PMC13726312", "id": "4f037bs7zxtbg", "issns": [ "1741-7015" ], "landing_url": "https://europepmc.org/article/MED/42972592", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "openalex", "2745|Systemic Lupus Erythematosus Research" ] ], "openalex": "W7172039043", "pdf_url": "https://europepmc.org/articles/PMC13726312?pdf=render", "pmcid": "PMC13726312", "pmid": "42972592", "published": "2026-07-31", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/4f037bs7zxtbg.ris", "sources": [ { "first_seen": "2026-11-04T15:20:45Z", "native_id": "MED:42972592", "source": "europepmc", "url": "https://europepmc.org/article/MED/42972592" }, { "first_seen": "2026-11-05T12:22:41Z", "native_id": "PMC13726312", "source": "pmc", "url": "https://doi.org/10.1186/s12916-026-05102-5" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2745|Systemic Lupus Erythematosus Research", "subfield": "general" } ], "title": "Defining the optimal interferon-stimulated genes panel to reflect serum interferon-α levels in patients with systemic lupus erythematosus.", "title_text": "Defining the optimal interferon-stimulated genes panel to reflect serum interferon-α levels in patients with systemic lupus erythematosus.", "type": "peer-reviewed", "updated_at": "2026-11-06T12:22:18Z", "url": "https://research.draconitic.com/paper/4f037bs7zxtbg", "venue": "BMC medicine", "versions": [] }