High Immunological Activity and the Re-Evaluation of Anti-SSA/SSB Antibodies as Prognostic Markers for Major Organ Damage in Systemic Lupus Erythematosus.

OBJECTIVE: Anti-SSA antibodies are among the most prevalent autoantibodies in systemic lupus erythematosus. While their association with cutaneous manifestations and neonatal lupus is established, their prognostic utility regarding long-term survival and major organ damage in adult SLE remains controversial, particularly in Asian populations. Furthermore, the added prognostic value of anti-SSB antibodies in anti-SSA-positive patients is debated. This study aimed to evaluate the impact of anti-SSA status on clinical phenotypes and long-term outcomes and to assess whether double positivity (anti-SSA+/SSB+) confers additional risk compared to single positivity (anti-SSA+/SSB-).

METHODS: We conducted a retrospective cohort study of 511 SLE patients at a medical center in Taiwan. Patients were stratified into anti-SSA positive (n = 331) and anti-SSA negative (n = 180) groups. We compared clinical characteristics, serological profiles, disease activity (SLEDAI), and long-term outcomes, including mortality, end-stage renal disease (ESRD), and interstitial lung disease (ILD). A subgroup analysis was performed to compare single positive versus double positive patients.

RESULTS: Anti-SSA positive patients were predominantly female (92.7% vs. 81.7%, p < 0.001) and exhibited significantly higher disease activity (SLEDAI: 13.8 ± 6.5 vs. 12.1 ± 6.0, p = 0.003). Immunologically, the anti-SSA positive group displayed a distinct "multiple autoantibody positivity" profile, characterized by a higher prevalence of anti-dsDNA (74.6% vs. 65.0%, p = 0.028), anti-Sm (44.1% vs. 22.8%, p < 0.001), and anti-RNP (48.3% vs. 31.7%, p < 0.001), along with lower C3 and C4 levels. However, despite this active serological profile, there were no significant differences between anti-SSA positive and negative groups regarding all-cause mortality (16.3% vs. 20.6%, p = 0.282), ESRD (10.0% vs. 8.3%, p = 0.655), or ILD (5.4% vs. 4.4%, p = 0.781). Multivariable regression models confirmed that anti-SSA status was not an independent predictor for mortality (adjusted Hazard Ratio [aHR] 0.82, p = 0.376), ESRD (adjusted Odds Ratio [aOR] 1.17, p = 0.654), or ILD (aOR 1.52, p = 0.369).

CONCLUSION: In this Asian SLE cohort, anti-SSA positivity served as a marker for a phenotype characterized by high immunological activity and multiple autoantibody positivity but was not significantly associated with poor long-term survival or irreversible organ damage in this cohort. However, larger studies are required to definitively exclude modest prognostic effects. The presence of anti-SSB antibodies provided limited additional prognostic value for adult outcomes, suggesting that risk stratification should focus on the primary driver, anti-SSA.