A groundbreaking development in the prevention of congenital heart block, a rare but devastating condition affecting newborns, has emerged from the research laboratories of NYU Langone Health. This life-threatening disorder, medically known as cardiac neonatal lupus, primarily afflicts infants born to mothers who carry anti-SSA/Ro antibodies—autoantibodies that can cross the placental barrier and interfere with the fetal heart’s electrical conduction system. This interference manifests as a dangerously slowed heart rate and often necessitates the implantation of a permanent pacemaker for the child’s survival.
Scientists at NYU Langone Health have, for the first time ever, demonstrated the successful use of rozanolixizumab—a neonatal Fc receptor (FcRn) inhibitor monoclonal antibody—to prevent the placental transfer of these harmful maternal autoantibodies. This pioneering approach specifically targets the FcRn receptors expressed on the placenta, which normally mediate the transport of IgG antibodies from mother to fetus. By blocking these receptors, rozanolixizumab effectively reduces the fetal exposure to pathogenic antibodies without compromising the overall immunological defense.
The clinical breakthrough came about through the close monitoring and treatment of a pregnant woman diagnosed with systemic lupus erythematosus, who possessed significantly elevated levels of anti-SSA/Ro antibodies. This patient had a history of two pregnancies complicated by congenital heart block; tragically, one offspring was lost before birth while the other survived but required a pacemaker shortly postpartum. Recognizing the urgency and dire need for intervention, researchers obtained approval under compassionate drug use protocols to administer rozanolixizumab during her pregnancy.
Treatment was initiated at gestational week 14, continuing through week 28—a critical window when the fetal heart is most susceptible to injury from autoimmune attacks. Weekly injections of rozanolixizumab were administered, accompanied by rigorous fetal cardiac surveillance through ultrasound imaging and at-home heart rhythm monitoring. The meticulous clinical assessment ensured real-time evaluation of any emerging cardiac conduction abnormalities.
Results were both encouraging and unprecedented. The treated pregnancy culminated in the delivery of a healthy female infant at 37 weeks, weighing approximately 2.89 kilograms. Impressively, the newborn exhibited no cardiac conduction defects typically associated with congenital heart block. Meanwhile, the mother tolerated the treatment remarkably well, experiencing no serious adverse effects. Notably, maternal autoantibody titers decreased by over 50 percent during therapy, underscoring the dual benefit of rozanolixizumab in both preventing transplacental antibody passage and diminishing systemic autoantibody burden.
This study, published in the Annals of the Rheumatic Diseases, represents a paradigm shift in neonatal lupus prevention. “Our findings provide compelling proof-of-concept that obstructing FcRn-mediated autoantibody transmission holds therapeutic promise,” stated Philip M. Carlucci, MD, the lead investigator. Dr. Carlucci emphasized the broader implications of this modality, suggesting that achieving “no autoantibodies equals no congenital heart block” could revolutionize prenatal care for high-risk pregnancies.
Jill Buyon, MD, the senior study investigator and director of the Lupus Center at NYU Langone, echoed this sentiment by highlighting the translational significance of the research. She announced the initiation of AVERT (Atrioventricular Block Elimination with Rozanolixizumab Therapy), a forthcoming multicenter clinical trial sponsored by the National Institutes of Health. This expansive study aims to evaluate the efficacy and safety of rozanolixizumab in a cohort of pregnant women who have previously delivered offspring affected by congenital heart block, thereby striving to confirm these initial promising findings.
Rozanolixizumab’s mechanism extends beyond placental blockade, also catalyzing the degradation of circulating IgG autoantibodies within the maternal bloodstream, thereby mitigating ongoing autoimmune activity. Originally approved by the U.S. Food and Drug Administration for treating myasthenia gravis—a chronic autoimmune neuromuscular condition—this drug’s repurposing illustrates the versatility and potential of FcRn inhibition in various immune-mediated diseases.
The collaborative investigation engaged an expert team spanning multiple institutions, including NYU Langone, Columbia University, the University of Arizona, Arthritis and Rheumatism Associates in Washington, D.C., and Children’s National Hospital. Their interdisciplinary expertise facilitated comprehensive clinical evaluation and robust data interpretation. The study received generous funding support from private donors Lauren and Andy Levison, alongside substantial grants from NIH branches dedicated to reproductive health and autoimmune disease research.
This landmark case study sets a precedent for novel immunomodulatory strategies in fetal medicine where maternal autoimmunity poses life-threatening risks to offspring. It opens new frontiers by demonstrating that targeted molecular therapies can intercept the pathological maternal-fetal antibody transfer pathway, possibly circumventing the need for postnatal invasive interventions such as pacemaker implantation.
While the results from this single-patient study warrant cautious optimism, they undeniably herald a transformative leap in clinical immunology and perinatal care. Continued investigation through the AVERT trial and subsequent research will be critical in validating rozanolixizumab’s role as a standard prophylactic agent against congenital heart block. The implications extend beyond neonatal lupus, offering a framework for managing other transplacental antibody-mediated fetal diseases.
In conclusion, the NYU Langone Health team’s pioneering use of rozanolixizumab heralds a promising era in the prevention of cardiac neonatal lupus, offering hope to families affected by this catastrophic condition. By intercepting the maternal autoantibodies at the molecular level, this therapeutic innovation aims to safeguard fetal heart health and improve survival outcomes, marking a significant advance in personalized prenatal medicine.
Subject of Research: People
Article Title: Blocking the neonatal Fc receptor as a novel approach to prevent cardiac neonatal lupus: a proof-of-concept study
News Publication Date: 18-Oct-2025
Web References: 10.1016/j.ard.2025.09.011
Keywords: Lupus, Congenital heart disease
