Extremely High Maternal Anti-Ro/La Antibody Titers Predict Non-Cardiac Neonatal Lupus Erythematosus Manifestations

Objectives Neonatal lupus erythematosus (NLE) is an autoimmune disease with diverse clinical manifestations, passively acquired through the transplacental transfer of maternal anti-Ro and/or anti-La antibodies (Ab). Higher maternal anti-Ro Ab titers have been associated with cardiac NLE, but the relationship between anti-Ro/La titers and non-cardiac NLE is currently unexplored. We hypothesize that anti-Ro Ab titer is associated with non-cardiac NLE. Methods Participants were identified from the SickKids NLE clinic, born between 2012 and 2019, to mothers with positive anti-Ro Ab titers within 1 year and 6 months of their child’s birth. We included the first child seen in the NLE clinic per mother. Clinical details were extracted from the NLE database supplemented by retrospective chart review of both infants and mothers. Ab titers were measured using enzyme-linked immunosorbent assay (ELISA) or chemiluminescent immunoassay (CIA), classified as high (ELISA: 8-100 U/mL, CIA: 20-1685 CU anti-Ro52, 20-1375 CU anti-Ro60) or extremely high (anti-Ro/La titer exceeded upper limit of detection). We excluded infants with cardiac NLE, and tested associations between maternal titer and infant NLE manifestations, jointly adjusting for infant sex, ethnicity, maternal HCQ use during pregnancy, extremely high anti-La Ab titer, and maternal rheumatic disease status. Results We identified 282 infants; 59% of mothers had extremely high anti-Ro titers. Hepatitis (27%) was the most prevalent NLE manifestation, followed by cytopenias (24%), rash (12%), and macrocephaly (4%). We excluded 24 infants with cardiac NLE. We observed a significant association between extremely high anti-Ro Ab titer and presence of any non-cardiac NLE manifestations (OR: 1.78, 95% CI 1.06-3.00, P=0.028) (Table), and extremely high anti-La Ab titer and cutaneous NLE (OR: 4.17, 95% CI 1.68-10.15, P=0.002), in multivariable adjusted models. Table. Association between extremely high anti-Ro/La antibodies and non-cardiac NLE manifestations Conclusion Extremely high maternal anti-Ro Ab titer was significantly associated with non-cardiac NLE, and anti-La Ab titer with cutaneous NLE. These associations were significant after adjusting for extremely high titers of the alternate autoantibody and other potential risk factors for NLE. Our findings have important clinical implications, informing family counseling and improving care for infants at risk of NLE and their families. Best Abstract on Research by an Undergraduate Student Award