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.


METHODS
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 (beta(2)-microglobulin), and soluble HLA-G2, which consists only of heavy chains, was achieved by substituting a monoclonal antibody that requires beta(2)-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.


CONCLUSIONS
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.
Hunt
J S
JS
Departments of Anatomy and Cell Biology and Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160-7400, USA.
Jadhav
L
L
Chu
W
W
Geraghty
D E
DE
Ober
C
C
D000818:Animals; D000911:Antibodies, Monoclonal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005865:Gestational Age; D006680:HLA Antigens / Q000097:blood*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000276:immunology; D012680:Sensitivity and Specificity; D012995:Solubility
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I