Developmental and synaptic defects caused by transplacental transmission of NMDA receptor antibodies

Autoantibodies (ABs) against neuronal proteins may severely impact the developing brain during pregnancy. ABs are actively transported across the placenta, and the immature blood-brain barrier provides access to the developing brain. We recently identified several non-encephalitic mothers with serum autoantibodies against NMDA receptors (NMDARs) who delivered babies with various neurodevelopmental disorders. In this project, we address the question if maternofetal transfer of anti-neuronal autoantibodies is pathogenic by inducing neurodevelopmental defects. This would represent a new pathomechanism of acquired congenital disorders. We will apply a wide spectrum of epidemiological, behavioral, molecular biological, and physiological techniques in a murine passive-transfer model as well as human cohorts. Even if the proposed pathogenic link were rare, identification of mothers positive for such ABs would enable new treatments aimed at preventing AB transfer and reducing or preventing life-long neuropsychiatric morbidity in the children.