Soluble HLA-G circulates in maternal blood during pregnancy

Objective: Soluble isoforms of the HLA class Ib gene HLA-G have been identified at the maternal-fetal interface. Because soluble forms of other HLA class I antigens modulate T-cell reactivity and induce cellactivated apoptosis, our goal was to determine whether soluble HLA-G circulates in maternal or fetal blood and to identify the specific isoform. Study Design: Capture enzyme-linked immunosorbent assays with mouse monoclonal antibodies directed toward an epitope present on all isoforms of soluble HLA-G were constructed to identify soluble HLA-G in 44 serum samples from nonpregnant control subjects, 129 serum samples from pregnant women, and 10 samples of term cord blood. Distinguishing between soluble HLA-G1, which is composed of heavy chains complexed with light chains (β2-microglobulin), and soluble HLA-G2, which consists only of heavy chains, was achieved by substituting a monoclonal antibody that requires β2-microglobulin for binding (W6/32) in the capture phase of the enzyme-linked immunosorbent assay. Results: Capture enzyme-linked immunosorbent assays with mouse anti–soluble HLA-G showed that soluble HLA-G was present at all stages of gestation and that levels of soluble HLA-G were statistically significantly higher in serum samples from pregnant women than in serum samples from nonpregnant women. In contrast, W6/32 failed to detect soluble HLA-G in serum samples from pregnant women. Cord serum samples did not contain detectable soluble HLA-G. Conclusion: Collectively, the data indicate that pregnancy is characterized by the presence of soluble HLA-G circulating in maternal blood and strongly suggest that the major isoform is soluble HLA-G2. (Am J Obstet Gynecol 2000;183:682-8.)