Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA + individuals without a systemic autoimmune rheumatic disease diagnosis

• Published in: Arthritis research & therapy Vol. 25; no. 1; p. 21
• Main Authors: Kim, Sonya T, Muñoz-Grajales, Carolina, Dunn, Shannon E, Schneider, Raphael, Johnson, Sindhu R, Touma, Zahi, Ahmad, Zareen, Bonilla, Dennisse, Atenafu, Eshetu G, Hiraki, Linda T, Bookman, Arthur, Wither, Joan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-02-2023; BioMed Central; BMC
• Subjects: Antibodies, Antinuclear; Arthritis; Autoimmune Diseases; Biomarkers; Cytokines; Development and progression; Diagnosis; Disease; Disease Progression; Ethnicity; Gene expression; Health aspects; Health care networks; Humans; Interferon; Interferon-alpha; Laboratories; Medical diagnosis; Pre-clinical; R&D; Research & development; Rheumatic Diseases; Rheumatoid arthritis; Risk factors; Systemic autoimmune rheumatic diseases; White people; Canada; United States > US; Pre-clinical; Systemic autoimmune rheumatic diseases; Interferon; Cytokines
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-023-02997-w

Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA
) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA
individuals and investigated their utility as biomarkers of clinical progression.
A total of 280 subjects were studied, including 50 ANA
healthy controls, 160 ANA
individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA
individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors.
Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA
individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%.
Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA
individuals at high risk of imminent symptomatic progression.