Vitamin D Is Associated With Susceptibility and Disease Severity in Systemic Lupus Erythematosus: A Systematic Review and Meta‐Analysis

ABSTRACT Objectives Vitamin D, recognized for its immunomodulatory properties, is potentially associated with autoimmune diseases like systemic lupus erythematosus (SLE). This systematic review and meta‐analysis assessed the relationship between Vitamin D levels and SLE, highlighting its role in modulating disease activity and immunological markers like anti‐dsDNA, C3, and C4. Methods Case–control studies reporting Vitamin D, disease activity indices, C3, C4, and anti‐dsDNA antibody levels in SLE patients and healthy controls were evaluated. Systematic searches in PubMed, Scopus, ScienceDirect, Web of Science, and Embase were last updated on April 6, 2024. Inclusion criteria targeted studies on SLE patients and healthy controls reporting these specific markers. Study quality was assessed with the Newcastle‐Ottawa Scale (NOS), and publication bias was checked using Egger's test and Begg's funnel plot. The meta‐analyses were conducted with CMAv4. Results Analysis of 43 studies with 2940 SLE patients and 2458 healthy controls showed significantly lower Vitamin D levels in SLE patients (mean difference: −10.070 ng/mL; 95% CI: −12.85 to −7.28; p < 0.001). Vitamin D levels negatively correlated with SLEDAI scores (correlation: −0.427; 95% CI: −0.541 to −0.298; p < 0.001) and anti‐dsDNA antibodies (correlation: −0.397; 95% CI: −0.611 to −0.130; p = 0.004), and positively correlated with complement components C3 (correlation: 0.268; 95% CI: 0.077–0.440; p = 0.006) and C4 (correlation: 0.299; 95% CI: 0.192–0.400; p < 0.001). Sensitivity analyses confirmed these findings. Conclusions The findings revealed a strong association between low Vitamin D levels and increased SLE severity. However, limitations like some inconsistency, small‐study biases, and possible language restrictions in study inclusion necessitate cautious interpretation.