Background

Systemic Lupus Erythematosus (SLE) exhibits marked sex-based difference. Understanding these sex-specific variations in clinical manifestations and autoantibody profiles, particularly within diverse ethnic cohorts like Chinese populations, is crucial for advancing personalized management strategies.

Methods

We retrospectively analyzed data from 1029 SLE patients (121 males, 908 females). Comprehensive immunological profiles, including complement C3, C4, CH50, antinuclear antibodies (ANA) titers and patterns, and antiphospholipid (aPL) antibodies, were assessed. Statistical analyses were performed to identify sex-specific prevalence and correlation patterns between autoantibodies and clinical indicators.

Results

Distinct autoantibody patterns emerged by sex. The speckled ANA pattern was more prevalent in males (84.1% vs 53.5%) and anti-Smith (Sm) antibodies were significantly higher in females (34.4% vs 19.8% in males; P = .001). No sex differences were found in ANA titers or aPL antibodies. Females had significantly lower complement levels and higher mean SLEDAI-2K scores (P < .001), while males showed more cardiovascular (P = .039) and pulmonary involvement (P = .026). Sex-specific correlations were evident: males displayed positive autoantibody-autoantibody correlations (e.g., anti-Sm vs anti-RNP), whereas females showed broader correlations, particularly between complement components and disease activity, serum creatinine, and anti-double-stranded DNA (dsDNA) antibodies, reflecting established markers of disease activity and renal involvement. Anti-Sm positivity linked to lower complement in both sexes. Notably, females with anti-Sm had increased anti-dsDNA positivity and elevated SLEDAI-2K, while males with anti-Sm showed higher 24-h urinary protein (P = .02), directly linking anti-Sm to renal involvement in males, a key aspect of male SLE severity.

Conclusions

This study highlights significant sex-based variations in autoantibody patterns and their clinical associations in a Chinese SLE cohort. The distinct prevalence of ANA patterns and anti-Sm antibodies, coupled with sex-specific immunological correlation networks, underscores the complex interplay of immune factors.