Unravelling the connection between interferons and systemic lupus erythematosus: a systematic review and...

Systemic lupus erythematosus (SLE) is characterized by dysregulated interferon (IFN) signaling. Despite its importance, a comprehensive and systematic synthesis of available data is lacking and findings across studies have been inconsistent. To address this gap, a systematic review and meta-analysis was conducted to evaluate global variations in IFNα, IFN-γ, and some important cytokines in adult SLE cases compared to healthy controls (HCs). Furthermore, we assessed their association with disease activity and effect of detection methods, sample types, and regional variations.

A systematic search was conducted in PubMed and Scopus as primary databases, with Google Scholar used as a supplementary search engine, using MeSH terms and keywords related to SLE and IFNs (up to 15 November 2024). The Quantitative synthesis was performed using Comprehensive Meta-Analysis, calculating standardized mean differences (SMD) with 95% confidence intervals (CI) using a random-effects model for continuous outcomes. Correlation data were analyzed using Fisher's z transformation. Publication bias was accessed using funnel plots and Egger's test. For heterogeneity, Cochrane's Q test, I² statistic, subgroup analyses, sensitivity analyses, and Bayesian meta-analysis were conducted.

A total of 33 eligible studies, comparing IFN levels among 2307 SLE patients and 1599 HCs were included. Significantly elevated levels of IFNα (SMD = 1.428, 95%CI [0.78, 2.08], p < 0.001) and IFNγ (SMD = 0.922, 95%CI [0.32, 1.52], p = 0.003) in SLE patients compared with HCs were observed. Elevated levels of IFNγ were correlated with disease activity (SMD = 0.609, 95%CI [0.30, 0.91], p < 0.001). Additionally, significantly elevated levels of key pro-inflammatory cytokines, including IL-6 (SMD = 0.679, 95%CI [0.45, 0.90], p < 0.001) and TNFα (SMD = 1.754, 95%CI [0.25, 3.26], p = 0.022), were observed. Subgroup analyses revealed that differences in detection method, sample type, and geographic regions could influence measured cytokine levels.

The elevated IFN levels in SLE patients, with a significant correlation of IFNγ with disease activity, suggest their role in disease pathogenesis and potential as a biomarker for monitoring disease activity. The findings identify IFNs and key pro-inflammatory cytokines as potential therapeutic targets. Given the limitations of our study, future research employing robust study designs and methodologies are warranted to increase the reliability of our findings.

PROSPERO CRD42023445357.