Autoimmune congenital heart block (CHB) represents a severe manifestation of neonatal lupus syndrome due to placental transfer of maternal anti-Ro/SS-A ± anti-La/SS-B autoantibodies, whereby type-I-interferon (IFN) activation is recognised as a significant risk factor for CHB development.1 2 However, only about 2% of children born to mothers with the respective antibodies are affected, indicating a disturbed feto-maternal tolerance in CHB pregnancies, which is still not entirely understood. Recent findings suggest a significant involvement of placental immune checkpoint molecules (CPM) in the induction of feto-maternal tolerance, in particular via the inhibitory molecule PD-L1, which is constitutively expressed in placental syncytiotrophoblasts juxtaposed to maternal blood and tissue.3 4 In line with this, the levels of soluble PD-L1 (sPD-L1) in the serum of pregnant women are higher than in non-pregnant women and are supposed to suppress maternal immunity.5 6 This study aims to assess the contribution of co-inhibitory and co-stimulatory checkpoint molecules in CHB affected and at-risk mothers positive for anti-Ro/SS-A ± anti-La/SS-B autoantibodies.

Therefore, in a first step, we analysed plasma from 12 pregnant women with CHB pregnancy and 23 with antibodies against Ro/SS-A ± La/SS-B without a CHB …