Soluble HLA-G in pregnancies complicated by autoimmune rheumatic diseases

Abstract

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance.

Keywords: Pregnancy; Rheumatic diseases; Soluble HLA-G.