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May 5, 2026

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

LLLi LiThe People's Hospital of Guangxi Zhuang Autonomous Region XTXi TanGuangxi Medical University CZChen ZhaoGuangxi Medical University

Key Points

The study aims to examine the relationship between plasma IL-33 levels and clinical features in systemic lupus erythematosus patients.
Cross-sectional study involving 133 SLE patients and 81 normal controls.
Plasma IL-33 levels measured via enzyme-linked immunosorbent assay.
Clinical parameters including SLEDAI-2K scores and skin lesions were collected.
SLE patients had significantly higher IL-33 levels (median 342.60 pg/ml) compared to controls (56.77 pg/ml, p < 0.0001).
IL-33 levels were positively associated with SLEDAI-2K scores (r = 0.279, p = 0.001) and skin lesions (p = 0.001).
Negative correlation with complement C3 (β = -0.303, p < 0.001) and positive correlation with IgA (β = 0.473, p < 0.001).

Abstract

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.

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