Abstract
Abstract
Background
The role of type I interferon (IFN-I) signaling in systemic lupus erythematosus (SLE) has been well established. However, unanswered questions remain regarding the applicability of these findings to pediatric-onset SLE. The aim of this review is to provide an overview of the novel discoveries on IFN-I signaling in pediatric-onset SLE.
Data sources
A literature search was conducted in the PubMed database using the following keywords: “pediatric systemic lupus erythematosus” and “type I interferon”.
Results
IFN-I signaling is increased in pediatric SLE, largely due to the presence of plasmacytoid dendritic cells and pathways such as cyclic GMP-AMP synthase–stimulator of interferon genes–TANK-binding kinase 1 and Toll-like receptor (TLR)4/TLR9. Neutrophil extracellular traps and oxidative DNA damage further stimulate IFN-I production. Genetic variants in IFN-I-related genes, such as IFN-regulatory factor 5 and tyrosine kinase 2, are linked to SLE susceptibility in pediatric patients. In addition, type I interferonopathies, characterized by sustained IFN-I activation, can mimic SLE symptoms and are thus important to distinguish. Studies on interferonopathies also contribute to exploring the pathogenesis of SLE. Measuring IFN-I activation is crucial for SLE diagnosis and stratification. Both IFN-stimulated gene expression and serum IFN-α2 levels are common indicators. Flow cytometry markers such as CD169 and galectin-9 are promising alternatives. Anti-IFN therapies, such as sifalimumab and anifrolumab, show promise in adult patients with SLE, but their efficacy in pediatric patients requires further investigation. Janus kinase inhibitors are another treatment option for severe pediatric SLE patients.
Conclusions
This review presents an overview of the IFN-I pathway in pediatric SLE. Understanding the intricate relationship between IFN-I and pediatric SLE may help to identify potential diagnostic markers and targeted therapies, paving the way for improved patient care and outcomes.
Graphical Abstract
Funder
National Key Research and Development Program of China
National High level Hospital Clinical Research Foundation
Publisher
Springer Science and Business Media LLC
Reference122 articles.
1. Psarras A, Emery P, Vital EM. Type I interferon-mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy. Rheumatology (Oxford). 2017;56:1662–75.
2. Crouse J, Kalinke U, Oxenius A. Regulation of antiviral T cell responses by type I interferons. Nat Rev Immunol. 2015;15:231–42.
3. Bezalel S, Guri KM, Elbirt D, Asher I, Sthoeger ZM. Type I interferon signature in systemic lupus erythematosus. Isr Med Assoc J. 2014;16:246–9.
4. Ronnblom L, Alm GV. An etiopathogenic role for the type I IFN system in SLE. Trends Immunol. 2001;22:427–31.
5. Jiang J, Zhao M, Chang C, Wu H, Lu Q. Type I interferons in the pathogenesis and treatment of autoimmune diseases. Clin Rev Allergy Immunol. 2020;59:248–72.