Molecular Human Reproduction, Vol. 9, No. 11, 729-735,
November 2003
© 2003 European Society of Human Reproduction and Embryology
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Immunogenicity of the soluble isoforms of HLA-G
Submitted on March 24, 2003; resubmitted on July 11, 2003. accepted on July 28, 2003
Departments of 1 Anatomy and Cell Biology, 2 Pathology and Laboratory Medicine and 3 Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA and 4 Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA
5 To whom correspondence should be addressed at: Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7400, USA. e-mail: jhunt{at}kumc.edu
Soluble class Ib HLA-G glycoproteins synthesized in the placenta are abundant in the pregnant uterus and circulate in maternal blood throughout pregnancy. To establish immunogenicity of these proteins, we tested sera from 64 women with at least one successful pregnancy (multigravid), 21 women who had never been pregnant, and 54 males for antibodies to epitopes present on recombinant sHLA-G isoforms (sHLA-G1, sHLA-G2) derived from HLA 6.0 cDNA (HLA-G*0101 allele). By indirect enzyme-linked immunosorbent assay, antibodies to sHLA-G isoforms were identified in six sera, all from multigravid women; all other sera were negative (P = 0.0083). Immunoblots showed that two of the positive sera reacted exclusively with sHLA-G1 and -G2 whereas four reacted to both sHLA-G and pooled HLA class I antigens. To establish potential relationships between anti-sHLA-G and exposure to foreign paternal alleles (*0101, *0103, *0104, *0106), all multigravid women and their partners were genotyped. No relationship between allelic disparity and antibody production was identified. Taken together, these results indicate that (i) tolerance to HLA-G is the usual condition as antibodies to HLA-G were not detected in 91% (58/64) multigravid women, and (ii) pregnancy stimulates loss of tolerance in 9% (6/64) of multigravid women. All six women delivered healthy babies, demonstrating that maternal antibodies to epitopes on sHLA-G do not abrogate pregnancy.
Key words: antibodies/HLA-G/immunity/pregnancy/tolerance
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