Exploring the Relationship between Serum IL-33 Levels and Clinical Manifestations in Systemic Lupus Erythematosus: A Comprehensive Analysis

<b>Aims/Background</b> Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterised by an unpredictable disease course and multifaceted clinical presentations. Recent studies have highlighted the potential role of interleukin-33 (IL-33) in autoimmune diseases, but its exact relationship with SLE remains unclear. Therefore, to investigate the role of serum IL-33 levels as a biomarker, we evaluated its correlation with disease activity and organ damage in SLE patients. <b>Methods</b> This retrospective analysis included 120 SLE patients from the Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Soochow University between January 2018 and December 2022. For comparative analysis, we recruited 60 healthy controls. Correlations between IL-33 levels and disease metrics were evaluated, and subgroup analyses were performed to explore specific clinical associations. <b>Results</b> Our findings revealed that SLE patients had significantly higher serum IL-33 levels than the control group (258.7 ± 103.5 pg/mL vs 78.3 ± 32.6 pg/mL, <i>p</i> < 0.001). Furthermore, IL-33 levels showed a significant association with both disease activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)) (r = 0.68, <i>p</i> < 0.001) and cumulative organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI)) scores (r = 0.45, <i>p</i> < 0.01). Notably, patients with active disease (SLEDAI ≥6) exhibited substantially elevated IL-33 levels (<i>p</i> < 0.001). Patients with organ damage (SLICC/ACR DI ≥1) demonstrated significantly higher IL-33 levels than those without organ damage (289.6 ± 95.3 pg/mL vs 234.1 ± 86.2 pg/mL, <i>p</i> = 0.001), and those with renal involvement showed higher IL-33 levels (<i>p</i> < 0.01). Receiver operating characteristic (ROC) curve analysis revealed better diagnostic potential of serum IL-33 levels for SLE (area under the curve (AUC) = 0.892, 95% confidence interval (CI): 0.845-0.939, sensitivity = 84.2%, specificity = 82.7%) and for identifying active disease (AUC = 0.816, 95% CI: 0.752-0.880, sensitivity = 77.8%, specificity = 75.0%). <b>Conclusion</b> Our findings suggest that serum IL-33 may serve as a promising biomarker for comprehensive SLE assessment, offering new avenues for monitoring disease progression and guiding therapeutic strategies.