Deep Serologic Profiling Identifies Novel Autoantibodies Associated with Fetal Atrioventricular Block

Poster presenter: Philip Carlucci, MD, Rheumatology Fellow, NYU Grossman School of Medicine

Poster title: Deep Serologic Profiling Identifies Novel Autoantibodies Associated with Fetal Atrioventricular Block

Poster session A: Saturday, Nov. 16

What is your poster about?
“Maternal anti-SSA/Ro52/60kD autoantibodies are necessary for the development of fetal atrioventricular block (AVB), but titers alone are not sufficient to predict the likelihood of AVB. Women with high titer and no prior affected offspring still face only a 4% risk of having a child with AVB. In search of biomarkers for more accurate risk assessment, we sought to identify novel autoantibodies associated with fetal AVB. To accomplish this, we applied a high-throughput antibody screen to samples collected from pregnant women prior to the development of AVB as part of the ongoing Surveillance and Treatment To Prevent Fetal Atrioventricular Block Likely to Occur Quickly (STOP BLOQ) study. This agnostic evaluation identified a signature of autoantibodies that could distinguish the pregnancies that went on to develop fetal AVB from matched pregnancies with healthy outcomes.”

Why did you decide to investigate this topic?
“Our poor ability to estimate the likelihood of fetal AVB leads to anxiety and a high economic burden as anti-Ro exposed pregnancies are currently managed by pediatric cardiologists with weekly or biweekly surveillance fetal echocardiograms. Even such management has become controversial since it is not settled who should have more intense monitoring. A better biomarker could provide reassurance to expectant women at low risk and avoid unnecessary surveillance. In addition, novel therapeutics such as monoclonal antibodies that block the neonatal Fc receptor (FcRn), preventing placental transport of antibodies, are currently in development. So, at this time, it is critical to identify factors that increase the risk of an anti-Ro positive woman to have a baby with AVB because there may finally be a prevention.”

What are you working on next related to this research?
“We plan to use the hundreds of samples collected from pregnancies in the STOP BLOQ study and in the NYU Research Registry for Neonatal Lupus (RRNL) to validate our findings from the discovery cohort. Simultaneously, we are leveraging additional high-throughput technologies to assess whether other soluble proteins might also serve as predictive biomarkers.”

What excites you most about your work?
“Additional risk factors for fetal AVB have remained elusive for decades. However, advancements in deep proteomic profiling technologies have significantly enhanced our ability to conduct analyses with high fidelity on an unprecedented scale. At the same time, we have continued to grow the archived collection of samples available for study and novel therapies may soon be evaluated. With this convergence of cutting-edge technology and clinical advancements, we are well positioned to make groundbreaking discoveries that could alleviate the burden of this devastating condition.”

What are you most looking forward to at ACR Convergence 2024 in Washington, D.C.?
“I am really looking forward to seeing all the exciting research updates at this year’s ACR meeting and connecting with colleagues from outside institutions.”