Such maternal immunological imprinting and in-utero exposure of the fetus resulting in adverse pregnancy outcomes are best exemplified in pregnancies with autoimmune conditions such as APS, SLE, myasthenia gravis and primary Sjögren’s syndrome. Risks for fetus and neonate Patients with APS often have anti-phospholipid autoantibodies that are reactive against phospholipid proteins, such as β2-glycoprotein, cardiolipin, tissue plasminogen activator, thrombin, protein C and platelet antigens. The pathogenicity of anti-phospholipid autoantibodies is often associated with IgG classes and they target proteins that are involved in thrombosis, platelet and complement pathway

activation, monocyte and endothelial cell functions MK-1775 mouse [75]. These autoantibodies can be either agonistic or antagonistic in nature. They contribute to the pathologies of APS by promoting thrombotic events, impairing endothelial Gemcitabine cost cell function and provoking overt inflammatory responses in the maternal circulation and placental tissues. This may lead to vasoconstriction, impaired endothelial function and placental dysfunction that restrict blood supply to the placenta and result in placental ischaemia

and/or hypertensive disorders. Such a cascade of events can lead to a range of poor pregnancy outcomes such as RSA, IUGR, pre-eclampsia or stillbirth. Mild to moderate thrombocytopenia is common in APS, and this can worsen in pregnancy [9]. The causes of APS-associated thrombocytopenia are poorly understood: unlike immune thrombocytopenia (ITP), specific antibodies against the major platelet adhesion receptors (GPIIb-IIIa or GPIb-V-IX) are uncommon. Pregnant

women with SLE carry not only a risk of maternal and fetal morbidity, but also risks of long-term disability to the newborn. The immunopathologies of SLE pregnancy display several features of those seen in APS. Thus, it is not surprising that SLE pregnancy shares many of the adverse risks and poor outcomes of APS, such as maternal morbidity, IUGR, pre-eclampsia, stillbirth or preterm birth [9]. In addition, the autoimmune conditions of SLE and APS are often exacerbated during pregnancy and contribute further to the disease burden and DOK2 dysfunction of the maternal circulation and renal system. The deposition of anti-nuclear proteins, anti-dsDNA, anti-basement membrane autoantibodies and autoreactive antibodies in kidney glomeruli can cause nephritis that results in further damage to the already compromised kidney function. This, in turn, exacerbates the hallmark signs of pre-eclampsia, such as hypertension and proteinuria. In addition, neonates of mothers with SLE or primary Sjögren’s syndrome are at risk of developing neonatal lupus syndrome and congenital heart block [9, 10]. These neonatal conditions often occur in mothers who are seropositive for anti-Ro/SSA and/or anti-La/SSB autoantibodies.