HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion.
Spontaneous abortion is the most common complication of human pregnancy. Natural killer (NK) cells expressing killer immunoglobulin-like receptors (KIRs), which may recognize HLA-C (i.e. its C1 or C2 groups) on trophoblast cells, constitute a large leukocyte population in the endometrium. This study investigated whether genetic polymorphisms in the KIR and HLA-C genes are risk factors for spontaneous abortion. One hundred and twenty-five couples with at least two spontaneous abortions, including eighty-five couples with idiopathic recurrent abortion (RSA; three or more abortions), and 117 control couples (with two or more healthy-born children) were tested. The frequencies of the individual KIR genes in the patients were similar to those in the controls. In the group of KIR AA women with HLA-C C2C2 partners, the HLA-C C1C2 heterozygotes were present in the controls but not in the patients (p=0.015 for all patients and p=0.0048 for RSA, but both comparisons lost significance after Bonferroni correction), whereas both homozygotes, C1C1 and C2C2, were absent in the control women but present among the aborting ones. Therefore, our results suggest that among KIR AA women who have HLA-C C2C2 partners, HLA-C heterozygous females show a trend towards an increased chance of successful pregnancy.
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114 Wrocław, Poland. izan@iitd.pan.wroc.pl
Izabela
I
Nowak
Andrzej
A
Malinowski
Henryk
H
Tchórzewski
Ewa
E
Barcz
Jacek R
JR
Wilczyński
Małgorzata
M
Banasik
Marian
M
Gryboś
Maciej
M
Kurpisz
Wioleta
W
Luszczek
Edyta
E
Majorczyk
Andrzej
A
Wiśniewski
David
D
Senitzer
Ji Yao
JY
Sun
Piotr
P
Kuśnierczyk
D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology; D004717:Endometrium / Q000276:immunology; D000939:Epitopes; D005260:Female; D005787:Gene Frequency; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D054340:Receptors, KIR / Q000235:genetics*; D012307:Risk Factors; D014327:Trophoblasts / Q000276:immunology
D000939:Epitopes; D015236:HLA-C Antigens; D054340:Receptors, KIR