Genetics of Neonatal Lupus Erythematosus Risk and Specific Manifestations

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Neonatal lupus erythematosus (NLE) is a condition where infants develop autoimmune symptoms due to maternal autoantibodies (anti-Ro/anti-La).
• The role of genetic predisposition in NLE risk among infants and mothers is not fully understood.

Purpose of the Study:

• To investigate the association between genetic factors, specifically polygenic risk scores (PRS) for systemic lupus erythematosus (SLE), and the risk of NLE in infants.
• To analyze the genetic contributions of both the infant and the anti-Ro antibody-positive mother to NLE development.

Main Methods:

• Genotyping was performed on infants and mothers using the Global Screening Array.
• Additive non-HLA and HLA polygenic risk scores (PRS) for SLE were calculated.
• Logistic regression and generalized linear mixed models were used to test associations between PRS and NLE outcomes (any NLE, cardiac NLE, cutaneous NLE).
• HLA-wide association analyses were also conducted.

Main Results:

• The study included 332 infants and 270 anti-Ro antibody-positive mothers.
• No significant associations were found between infant PRS, maternal PRS, or the difference in PRS between mother and infant, and any NLE outcomes.
• HLA-wide analyses did not identify specific NLE risk alleles.

Conclusions:

• In this multiethnic cohort, SLE genetic risk, as measured by PRS, was not significantly associated with the development of NLE manifestations in infants born to anti-Ro antibody-positive mothers.
• Further research may be needed to explore other genetic or environmental factors influencing NLE risk.