The pathogenic role of high-titer anti-Ro52 antibodies in neonatal lupus erythematosus: insights from a 9 case series

Background Neonatal Lupus Erythematosus (NLE) is a rare acquired autoimmune disease caused by the transplacental transfer of maternal anti-Ro/SSA and anti-La/SSB antibodies. Despite the high prevalence of these antibodies in mothers with Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the clinical manifestations in neonates are highly heterogeneous, ranging from transient cutaneous lesions to life-threatening congenital heart block (CHB). Methods This study analyzed a case series of nine mother-infant pairs diagnosed with NLE. We integrated clinical outcomes, maternal serological profiles (including quantitative anti-Ro52, Ro60, and La titers), and pharmacological interventions to explore the determinants of disease severity and organ-specific manifestations. Results Among the nine mothers, six (66.7%) had Sjögren's syndrome and three (33.3%) had systemic lupus erythematosus, including two with secondary antiphospholipid syndrome. Notably, 88.9% of mothers were diagnosed with autoimmune disease during or after the affected pregnancy. All mothers demonstrated antinuclear antibody positivity and were uniformly positive for anti-SSA/Ro, anti-SSB/La, and anti-Ro52 antibodies. Cardiac involvement occurred in three pregnancies, including recurrent complete CHB leading to pregnancy termination in one mother. One fetus with second-degree atrioventricular block received prompt dexamethasone therapy and achieved successful reversal of conduction abnormalities. Cutaneous manifestations were observed in five neonates, while hematologic involvement, primarily thrombocytopenia and anemia, occurred in four cases. Maternal hypocomplementemia and elevated inflammatory markers appeared to be associated with more severe fetal outcomes. Conclusion All nine mothers (100%) tested positive for high-titer anti-Ro52 antibodies, a finding consistent with the proposed role of anti-Ro52 as a risk biomarker for NLE. Intensive fetal echocardiographic surveillance between 16 and 26 weeks of gestation is vital to capture the critical window of low-degree conduction block, where synergistic immunomodulation with dexamethasone can reverse fetal heart block prior to irreversible nodal fibrosis. NLE serves as an early warning sign of occult maternal autoimmune disease, requiring long-term maternal follow-up.