Upregulated GLUT1 expression correlates with type I interferon activity and disease severity in cutaneous lupus erythematosus.

Background: The pathogenesis of cutaneous lupus erythematosus (CLE) is driven by the overactivation of the type I interferon (IFN-I) system. Although dysregulated glucose metabolism has been implicated in autoimmune inflammation, its role in CLE remains largely unexplored. This study aims to elucidate the role of glucose metabolism in CLE, specifically exploring its correlation with IFN-I activity and its contribution to disease severity. Methods: Skin biopsies were obtained from 51 patients with active, untreated CLE - including two of its most prevalent subtypes: 26 with subacute cutaneous lupus erythematosus (SCLE) and 25 with discoid lupus erythematosus (DLE) - and 8 healthy controls. Glucose uptake and IFN-I system activation was evaluated via GLUT1 (SLC2A1) and MxA (MX1) immunohistochemistry, respectively. Disease activity was measured using the CLASI-A score. Publicly available transcriptomic datasets were analyzed using Spearman's rank correlation to evaluate the association between Results: GLUT1 expression was significantly increased in both CLE subtypes compared to healthy controls (SCLE: p = 0.0344, DLE: p = 0.0356). MxA expression in keratinocytes and lymphocytes was also markedly elevated in CLE samples (p = 0.0031, p = 0.0059). Keratinocyte GLUT1 expression positively correlated with keratinocyte and lymphocyte MxA expression (p = 0.003, r = 0.41; p < 0.001, r = 0.483) and with CLASI-A scores (p < 0.001, r = 0.47). Additionally, a significant positive correlation was observed between Conclusion: Our findings identify a link between elevated GLUT1 expression, IFN-I pathway activation, and CLE disease activity, suggesting that enhanced glucose metabolism may contribute to the immunopathogenesis and clinical severity of CLE.