Interferon Signature Genes in Early Diagnosis of Systemic Lupus Erythematosus: Current Value and Limitations

Abstract

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease, and early diagnosis remains a major clinical challenge. Abnormal activation of the type I interferon (IFN) pathway is one of the core mechanisms in the pathogenesis of SLE. The IFN signature, as a biomarker reflecting activation of this pathway, has received extensive attention in recent years. This review systematically summarizes the definition and detection methods of the IFN signature and research progress in its use for early diagnosis of SLE. For predicting conversion from undifferentiated connective tissue disease (UCTD) to SLE, current evidence shows that patients with incomplete SLE have significantly increased IFN scores that are closely related to autoantibody profiles, indicating its potential use as a risk stratification tool. For supplementary diagnosis in antinuclear antibody (ANA)-negative or low-positive patients, the IFN signature may provide additional differential information beyond traditional serological tests. In addition, the IFN signature also shows certain value in the differential diagnosis of SLE and other autoimmune diseases, but it must be judged comprehensively together with clinical and other laboratory indicators. However, clinical application of the IFN signature still faces multiple challenges, including insufficient threshold standardization, marked ethnic differences, inadequate longitudinal stability, and relatively high testing cost. This review considers that the IFN signature has a clear biological basis and preliminary clinical evidence as an auxiliary tool for early diagnosis of SLE, but it cannot currently be used alone for confirmed diagnosis. Future work should focus on establishing standardized testing systems, developing multidimensional composite scoring models, and exploring rapid point-of-care testing technologies to promote the translation of the IFN signature from the laboratory to clinical practice.