Misztal, Melissa C., Gold, Nick, Cao, Jingjing, Diaz, Talia, Dominguez, Daniela, Thompson, Kendal, Jaeggi, Edgar, Knight, Andrea M., Laskin, Carl, Ng, Lawrence, Silverman, Earl D., and Hiraki, Linda T.
ObjectiveNeonatal lupus erythematosus (NLE) is a passively acquired autoimmune disease in infants born to anti-Ro and/or anti-La autoantibody-positive mothers. Genetics may affect NLE risk. We analyzed the genetics of infants and anti-Ro antibody-positive mothers, with NLE and NLE-specific manifestations.MethodsInfants and mothers from a tertiary care clinic underwent genotyping on the Global Screening Array. We created additive non-HLA and HLA polygenic risk scores (PRS) for systemic lupus erythematosus (SLE), from one of the largest genome-wide association studies. Outcomes were any NLE manifestations, cardiac NLE, and cutaneous NLE. We tested the association between SLE-PRS in the infant, mother, and the PRS difference between the mother and infant with NLE outcomes, in logistic regression and generalized linear mixed models (Bonferroni P< 0.02). We also performed HLA-wide analyses for the outcomes (P< 5.00 × 10–8).ResultsThe study included 332 infants, 270 anti-Ro antibody-positive mothers, and 253 mother-infant pairs. A large proportion of mothers (40.4%) and infants (41.3%) were European, and 50% of infants were female. More than half of the infants had NLE (53%), including 7.2% with cardiac NLE and 11.7% with cutaneous NLE. We did not identify significant associations between infant PRS, maternal PRS, or maternal-infant PRS difference and any NLE outcomes. HLA-wide analyses did not identify NLE risk alleles.ConclusionIn a multiethnic cohort of infants and anti-Ro antibody-positive mothers, we did not identify a significant association between SLE genetics and risk of NLE outcomes.