Evaluating the Diagnostic Potential of Myxovirus Resistance Protein 1 (MX1) and Myxovirus Resistance Protein 2 (MX2) As Biomarkers in Idiopathic Inflammatory Myopathies

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune muscle diseases characterized by proximal muscle weakness, systemic involvement, and high morbidity. Current diagnosis relies on clinical assessment, serology, and muscle biopsy, but challenges remain due to overlapping features and cases lacking clear biomarkers. Identifying molecular markers that reflect underlying disease pathways could improve diagnostic accuracy and patient stratification. This systematic review evaluates the diagnostic potential of myxovirus resistance protein 1 (MX1) and myxovirus resistance protein 2 (MX2), two interferon-inducible genes, as biomarkers in IIM and related conditions. A comprehensive literature search of PubMed, Embase, Web of Science, Ovid, and CINAHL (2015-2025) identified studies examining MX1 and/or MX2 in muscle disease. Eligible studies assessed diagnostic accuracy, sensitivity, specificity, or clinical relevance. Data extraction and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Joanna Briggs Institute guidelines. Evidence suggests that MX1 is consistently elevated in affected muscle tissue in IIM, particularly dermatomyositis, where it demonstrates high tissue specificity, though its expression is not exclusive to this subtype. Peripheral or blood-based MX1 measurements show promise but risk false positives and are influenced by disease activity, prior treatment, and timing of sampling. MX2 is consistently upregulated at the transcriptomic level, but protein-level data are limited, and its incremental diagnostic value over MX1 remains unclear. Sensitivity and specificity vary across studies, emphasizing the need for standardized protocols and further benchmarking against other interferon-inducible biomarkers or clinical tools. Overall, MX1 is a valuable tissue biomarker for interferon-mediated myopathies, with potential applications in diagnosis, disease activity assessment, and monitoring systemic progression. Future prospective, multicenter, and longitudinal studies are required to validate these markers, address current limitations, and determine their utility in routine clinical practice.