Circulating IL-33 as a sensitive alarmin in systemic lupus erythematosus: a biomarker for disease activity and skin-specific manifestations

Interleukin-33 (IL-33), an alarmin predominantly released by keratinocytes and endothelial cells, plays a pivotal role in type 2 immune responses and has been linked to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to explore the relationship between plasma IL-33 levels and clinical features in SLE patients. A cross-sectional study was conducted involving 133 SLE patients and 81 normal controls. Plasma IL-33 levels were measured via enzyme-linked immunosorbent assay. Clinical parameters, such as SLEDAI-2K scores, photosensitivity, skin lesion distribution, laboratory indices, immunofluorescence and immunohistochemistry results were collected. SLE patients demonstrated significantly higher circulating IL-33 levels compared to healthy controls (median 342.60 pg/ml vs. 56.77 pg/ml, p < 0.0001). IL-33 levels were positively associated with SLEDAI-2K scores (r = 0.279, p = 0.001), photosensitivity (p = 0.02), and facial skin lesions (p = 0.001). The expression levels of the IL-33 receptor (ST2) in head and face cutaneous tissues were markedly higher than those in other anatomical regions and in normal control subjects (p < 0.001). Multivariate analysis revealed negative correlations with complement C3 (β = - 0.303, p < 0.001) and positive correlations with IgA (β = 0.473, p < 0.001) and hs-CRP (β = 0.310, p < 0.001). Notably, IL-33 levels were higher in male patients (p = 0.002) and treatment-naïve patients (p = 0.03). Our data associate circulating IL-33 with SLE activity, photosensitivity, and specific serological markers. For the association between IL-33 and cutaneous photosensitivity, this study provides further histological evidence. This finding provides a novel perspective on the mechanism of photosensitivity in SLE, demonstrating the potential of IL-33 as a biomarker for patient stratification management.