Study of the pathogenesis of congenital heart block (CHB) in anti-SSA antibodies exposed newborns
Concept
Pregnancies in women with primary Sjögren’s disease typically progress without issues, although newborns of anti-SSA antibodies positive mothers face a risk of congenital heart block (CHB), which lacks effective treatment options. Maternal anti-SSA antibodies affect fetal heart by triggering inflammation, fibrosis, and calcium regulation alterations, potentially leading to CHB. A translational PhD project will delve into three immunological axes, including type I IFN interaction with CHB susceptibility genes, identifying cardiac targets of anti-SSA auto-antibodies, and exploring inflammatory pathways in CHB pathogenesis. Previous studies connect CHB with short and long-term complications like growth retardation, cardiomyopathy, and cerebral infarction. The PhD project will integrate clinical assessment with molecular studies to understand CHB's mechanisms, aiming to identify biomarkers and eventually pave the way for the development of targeted therapies.
Facts and Figures
MD, MSc Grégoire Martin De Fremont
Assistance Publique des Hôpitaux de Paris
gregoire.martin-de-fremont@aphp.fr
Meet the Team
Project Lead
MD, MSc Grégoire Martin De FremontAssistance Publique des Hôpitaux de Paris
gregoire.martin-de-fremont@aphp.fr
Objectives
This PhD is a translational research project build to address basic immunological and clinical issues as follows:
The basic immunological project aims to:
- Objective 1: Investigate the interaction between type I IFN and CHB susceptibility genes
- Objective 2: Identify cardiac targets of anti-SSA auto-Abs
- Objective 3: Explore inflammatory pathways involved in the pathogenesis of CHB
The clinical project aims to:
- Objective 1: Study fetal and neonatal health of CHB newborns from anti-SSA+ mothers
- Objective 2: Study long-term outcome of CHB offspring from anti-SSA+ mothers
Goals/Milestones
By the end of the first year, the student is expected to:
- Have completed the experiments for objective 1 of the basic immunological project and be able to communicate about the preliminary results
- Have preliminary results for objective 3 of the basic immunological project
- Have completed the analysis of the dataset for the objective 1 of the clinical project and be able to submit a paper and communicate about the results
Patient Voice
Both immunological and clinical issues addressed in this project are meant to answer unmet needs in the field of autoimmune diseases and pregnancy and the project is expected to have tangible benefits for patients with anti-SSA Abs. First, it will help to define better pre-counseling guidelines for women with anti-SSA Abs and tailored fetal monitoring. The development of predictive markers for CHB could alleviate the psychological burden associated to a very frequent ultrasound monitoring in women with a low risk of CHB. Ultimately, a pre-emptive treatment in women identified with a high risk of CHB could prevent mortality and long-term comorbidities. Patients are highly valued in this project given their central role in investigating the pathogenesis of CHB. The participation of a large number of mothers who had blood sampling early in pregnancy and at delivery (paired maternal-fetal samples) is a key element of the project. To associate actively PRPs to the project, the student will regularly communicate them the progress of his research and discuss the next steps. Direct communication with patients in PRPs meeting can also be initiated, as previously done by student. The construction of a long-term partnership will hopefully help disseminate the results to a large number of women with anti-SSA Abs and a wish to conceive.