B Cell Interferon-Induced Transmembrane Protein 2: A Candidate Biomarker Associated with Disease Activity in Systemic Lupus Erythematosus

Background: Interferon-I (IFN-I) upregulates interferon-induced transmembrane protein 2 (IFITM2) expression, and elevated IFN-I levels are a hallmark of systemic lupus erythematosus (SLE). This study aimed to evaluate the association between IFITM2 expression and SLE pathogenesis. Given that dysregulated B cell differentiation and autoantibody production are key contributors to SLE and are further potentiated by IFN-I signaling, the involvement of relevant molecular pathways was also investigated. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 healthy controls (HCs) and 35 patients with SLE. IFITM2 expression in B cells was quantified by flow cytometry and analyzed for association with disease activity. Univariable analysis and receiver operating characteristic curve analyses were performed to evaluate the diagnostic performance of IFITM2 for identifying active SLE. Results: IFITM2 expression was significantly upregulated in B cells from SLE patients relative to healthy controls (HCs). Patients with active SLE displayed higher IFITM2 levels in total B cells and B cell subsets compared with those in inactive disease, and its expression was positively correlated with the SLEDAI-2K score. IFITM2 expression showed a positive association with concentrations of immunoglobulins, proinflammatory cytokines, and antinuclear antibodies, while inversely correlated with serum complement C3 and C4 levels. Combined assessment of IFITM2 and anti-dsDNA antibody levels enhanced discriminatory performance for SLE. Notably, IFITM2 expression was markedly higher in SLE patients with renal involvement than in those without renal involvement and exhibited a positive correlation with urinary total protein (UTP). Conclusions: B cell IFITM2 expression is closely associated with disease activity in SLE and may serve as a potential biomarker to improve the discriminatory performance of anti-dsDNA testing. Moreover, IFITM2 correlates with renal involvement (defined by proteinuria) in SLE and shows a positive correlation with UTP, suggesting that combined assessment of IFITM2 and UTP may help reflect renal status in patients with SLE. However, these findings are exploratory and require validation in independent cohorts before IFITM2 can be considered a clinically useful biomarker.