HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion

Nowak, Izabela; Malinowski, Andrzej; Tchórzewski, H; Barcz, Ewa; Wilczyński, Jacek R.; Banasik, Mirosław; Gryboś, Marian; Kurpisz, Maciej; Luszczek, Wioleta; Majorczyk, Edyta; Wiśniewski, Andrzej; Senitzer, David; Sun, Ji; Kuśnierczyk, Piotr

doi:10.1016/j.jri.2010.11.001

Cited by 29 publications

(31 citation statements)

References 41 publications

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“…They 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 [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

KIR Gene Frequencies in Women with Infertility Problems

Djulejic¹

2015

SEE J Immunol

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BACKGROUND: Natural killer (NK) cells are the predominant lymphocyte population in the decidua. Being the most abundant leucocytes, the activity of NK cells is important in different immuno-pathological conditions, such as recurrent spontaneous abortions, infertility and problems in implantation. The NK cells recognize HLA class I molecules on trophoblasts trough killer immunoglobulin-like receptors (KIRs) found on their surface. The KIRs are classified as either activating or inhibitory, regarding the effect they produce on NK cells upon interaction with corresponding ligand. Since KIR genes exhibit extensive polymorphism and individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes, it is hypothesized that the KIR gene content might influence the pregnancy outcome.

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“…They 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 [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

KIR Gene Frequencies in Women with Infertility Problems

Djulejic¹

2015

SEE J Immunol

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“…On the other hand, in a study of Faridi et al [5] from a North Indian population noticed that the patients with recurrent misscariage showed a higher prevalence of B haplotypes when compared with A haplotypes. In addition, recently Nowak et al [21] suggested that KIR AA and HLA-C heterozygous women who have HLA-C C2 homozygous partners showed an increased chance of successful pregnancy. In concordant with these findings, in our study we found a significantly higher frequency of Bx genotype in the study group and higher frequency of AA genotype in the control group.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of KIR genes in recurrent miscarriage

Öztürk

Şahin

Karaçor

et al. 2012

J Assist Reprod Genet

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Purpose Natural killer (NK) cells express killer immunoglobulinlike receptors (KIRs) which recognize HLA class I molecules on trophoblasts. KIRs could either activate NK cells or inhibit them to produce soluble factors necessary for the maintenance of pregnancy, thus they are suspected of being involved in the causes of recurrent miscarriage. The aim of this study was to evaluate whether there is any possible association between KIR genes, genotypes and recurrent miscarriage. Methods The present study was carried out on 40 women who had unexplained recurrent miscarriage and 90 controls. Sequence-specific oligonucleotide probes analysis were used to investigate 16 KIR genes. All data were statistically analyzed by Fisher Exact Test. Results The rate of Bx genotypes that consists elevated number of activating KIR genes was significantly higher (p00.014) in women with recurrent miscarriage when compared with the control group. Additionally, the frequency of AA genotype (AA1) of the subjects in the study group was significantly lower than the frequency of the subjects in the control group (p00,014). Furthermore, there were no statistically significant differences in the frequencies of the individual KIR genes between women with recurrent miscarriage and the control group. Conclusions Inclined balance of KIRs toward an activating state in NK cells may contribute to recurrent miscarriage.

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“…[66] HLA-G belongs to the subclass Ib, encompassing HLA-E, HLA-F, and HLA-G, and is highly expressed on trophoblast cells, which are much less polymorphic than the Class I genes [HLA-A and HLA-B are present in all the tissues except on the trophoblast cells, while HLA-C is expressed at a low level on the trophoblast and has indeed been associated with pregnancy disorders, such as preeclampsia and miscarriage, depending on the allelic complement of the killer cell inhibitory receptor (KIR) harbored by the maternal uterine Natural Killer (uNK) cells]. [67,68] A very interesting feature of HLA-G is that upon specific alternative splicing events, the soluble forms HLA-G5, HLA-G6, and HLA-G7 are released and may play a long-range immunomodulatory function. HLA-G is now considered as a reliable marker of the success of in vitro fertilization (IVF).…”

Section: "Wrong" Hla Programmingmentioning

confidence: 99%

Genetic regulation of recurrent spontaneous abortion in humans

Vaiman¹

2015

Biomed J

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Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus) and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases), thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene. rather attempt to categorize the factors that were analyzed according to their biological functions and summarize their putative effects.

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HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion

Cited by 29 publications

References 41 publications

KIR Gene Frequencies in Women with Infertility Problems

KIR Gene Frequencies in Women with Infertility Problems

Evaluation of KIR genes in recurrent miscarriage

Genetic regulation of recurrent spontaneous abortion in humans

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