Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

Abstract

Lupus is an autoimmune disease that primarily affects young women of childbearing age. Fertility rates in lupus patients depend on various factors, including disease activity, nephritis, and the presence of antiphospholipid antibodies; however, after lupus patients become pregnant, different factors may affect the course of pregnancy, such as the production of autoantibodies, pre-existing renal disease, and eclampsia, among others. The placenta is a temporary hemochorial organ that prevents immunological conflict due to exposure to alloantigens at the maternal-fetal interface; placental regulatory T cells play a major role in maternal-fetal tolerance. Typically, significant amounts of maternal IgG class antibodies cross the placenta and enter the fetal circulation. This transition depends on the distribution of Fc receptors along the syncytiotrophoblast. The production of antinuclear antibodies (ANA) is a hallmark of lupus, and these autoantibodies can form immune complexes that are typically trapped in the placenta during gestation. However, the entry of ANA into the fetal circulation depends on the IgG-ANA concentration and the FcR placental density. Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus if transfused by the placental pathway and could induce neonatal pathologies, such as neonatal lupus and congenital heart block. Here, we review the experimental and clinical data supporting a pathogenic role for maternal autoantibodies transmitted to the fetus.

Stratifying management of rheumatic disease for pregnancy and breastfeeding

“…These drugs share similar structure with maternal IgG, which are large proteins (~150 kDa) that are unable to diffuse across the placenta 99 . Active trans-placental transfer of maternal IgG takes place via neonatal Fc receptors on syncytiotrophoblast [100][101][102] and occurs rapidly from 16 weeks of pregnancy onwards (Figure 1). Some biologic DMARDs are fusion proteins containing part or none of the IgG structure , principally etanercept and abatacept.…”

Infants of mothers with systemic connective tissue disease – serological and clinical status in the first year of life; a pilot study

“…Transplacental transfer is possible in women with ANA antibodies during pregnancy [10][11][12][13]. These autoantibodies may cause damage to the developing tissues and increase the risk of bearing infants with neonatal lupus erythematosus (NLE).…”