Lack of the appropriate natural killer cell inhibitory receptors in women with spontaneous abortion.
Previous studies have revealed that women with unexplained recurrent spontaneous abortions have a limited repertoire of inhibitory KI receptors (inhKIRs) and that the inhKIRs they possess do not have specificity for the human leukocyte antigen (HLA)-Cw molecules that would be expressed on trophoblast. We sought to confirm these findings by direct definition of maternal inhKIR and trophoblastic HLA-Cw allotypes on the placental material of spontaneously missed pregnancies. The study included 30 women undergoing vacuum uterine curettage for first-trimester missed pregnancy (group A; n = 15) or for elective termination of normal pregnancy (group C, n = 15). DNA extracted from isolated decidual and trophoblastic cells was used for molecular detection of maternal inhKIRs (2DL1, 2DL2, 2DL3) and fetal HLA-Cw alleles, respectively. The results revealed that in the group of women who experienced abortion, 60% did not have the full repertoire of three inhKIRs (group A vs group C; p = 0.006); that in five of 15 patients (none in the controls), no epitope matching existed between maternal inhKIRs and trophoblastic HLA-Cw alleles (group A vs group C; p = 0.01); and that more cases were found with limited epitope matching (less than three inhKIRs with specificity for fetal HLA-Cw alleles). The results provide additional evidence that in some cases of spontaneous abortions, the women lack the appropriate inhKIRs to interact with the HLA-Cw molecules on trophoblasts and to deliver signals to inhibit natural killer cell activation and protect the embryo.
Varla-Leftherioti
M
M
Department of Immunobiology, Helena Venizelou Maternity Hospital, 11521 Athens, Greece. gr1bmdr@hol.gr
Spyropoulou-Vlachou
M
M
Keramitsoglou
T
T
Papadimitropoulos
M
M
Tsekoura
C
C
Graphou
O
O
Papadopoulou
C
C
Gerondi
M
M
Stavropoulos-Giokas
C
C
D000022:Abortion, Spontaneous / Q000276:immunology*; D003656:Decidua / Q000276:immunology; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology*
D015236:HLA-C Antigens; C446263:HLA-C*12:03 antigen; D011971:Receptors, Immunologic