KIR and HLA-C genes in male infertility

Wilczyńska, Karolina; Radwan, Paweł; Krasiński, Rafał; Radwan, Michał; Wilczyński, Jacek R.; Malinowski, Andrzej; Barcz, Ewa; Nowak, Izabela

doi:10.1007/s10815-020-01814-6

Cited by 6 publications

(6 citation statements)

References 44 publications

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“…Genomic DNA was isolated from venous blood using the Invisorb Spin Blood Midi Kit (Invitek, Germany) or QIAamp DNA Mini Kit (Qiagen, Germany) according to the manufacturer's instructions. KIRs were genotyped using KIR Ready Gene kits (Inno-train Diagnostics, Germany) following the manufacturer's instructions [for details, see reference (42) and Table 2)] or multiplex PCR described elsewhere (43,44). Our KIR typing was validated three times per year by the International KIR Exchange program organized by the Immunogenetics Center of the University of California, Los Angeles.…”

Section: Dna Preparation and Genotypingmentioning

confidence: 99%

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure

Piekarska

Radwan²,

Tarnowska

et al. 2021

Front. Immunol.

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The mother’s uterine immune system is dominated by uterine natural killer (NK) cells during the first trimester of pregnancy. These cells express killer cell immunoglobulin-like receptors (KIRs) of inhibitory or activating function. Invading extravillous trophoblast cells express HLA-C molecules, and both maternal and paternal HLA-C allotypes are presented to KIRs. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) shape the HLA class I immunopeptidome. The ERAPs remove N-terminal residues from antigenic precursor peptides and generate optimal-length peptides to fit into the HLA class I groove. The inability to form the correct HLA class I complexes with the appropriate peptides may result in a lack of immune response by NK cells. The aim of this study was to investigate the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in recurrent implantation failure (RIF). In addition, for the first time, we showed the results of ERAP1 and ERAP2 secretion into the peripheral blood of patients and fertile women. We tested a total of 881 women. Four hundred ninety-six females were patients who, together with their partners, participated in in vitro fertilization (IVF). A group of 385 fertile women constituted the control group. Women positive for KIR genes in the Tel AA region and HLA-C2C2 were more prevalent in the RIF group than in fertile women (p/pcorr. = 0.004/0.012, OR = 2.321). Of the ERAP polymorphisms studied, two of them (rs26653 and rs26618) appear to affect RIF susceptibility in HLA-C2-positive patients. Moreover, fertile women who gave birth in the past secreted significantly more ERAP1 than IVF women and control pregnant women (p < 0.0001 and p = 0.0005, respectively). In the case of ERAP2, the opposite result was observed; i.e., fertile women secreted far less ERAP2 than IVF patients (p = 0.0098). Patients who became pregnant after in vitro fertilization embryo transfer (IVF-ET) released far less ERAP2 than patients who miscarried (p = 0.0032). Receiver operating characteristic (ROC) analyses indicate a value of about 2.9 ng/ml of ERAP2 as a point of differentiation between patients who miscarried and those who gave birth to a healthy child. Our study indicates that both ERAP1 and ERAP2 may be involved in processes related to reproduction.

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Section: Dna Preparation and Genotypingmentioning

confidence: 99%

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure

Piekarska

Radwan²,

Tarnowska

et al. 2021

Front. Immunol.

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“…KIR receptors play an important role in the control of NK cell function. They are receptors present on the surface of natural cytotoxic cells and certain subpopulations of T cells: γδ, αβ, CD8+, and CD4+ [ 61 , 62 , 63 ]. Because both KIR receptors and MHC class I antigens are highly polymorphic, their interactions differentiate and individualize the NK cell response [ 64 ].…”

Section: Structure Of Kir Receptorsmentioning

confidence: 99%

“…Fertile men differ in their KIR gene profile and KIR–HLA-C combinations from men entering IVF treatment. Potential integrations between activating KIR receptors in CenAB + BB carriers and HLA-C allotypes may influence male infertility, while carriers of the KIR CenAA genotype do not experience problems with conception [ 61 ].…”

Section: Research Reviewmentioning

confidence: 99%

Immunological Aspects of Infertility—The Role of KIR Receptors and HLA-C Antigen

Wasilewska,

Grabowska,

Moskalik-Kierat

et al. 2023

Cells

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The mechanisms of immune tolerance of a mother against an antigenically foreign fetus without a concomitant loss of defense capabilities against pathogens are the factors underlying the success of a pregnancy. A significant role in human defense is played by killer immunoglobulin-like receptor (KIR) receptors, which regulate the function of the natural killer (NK) cells capable of destroying antigenically foreign cells, virus-infected cells, or tumor-lesioned cells. A special subpopulation of NK cells called uterine NK cells (uNK) is found in the uterus. Disruption of the tolerance process or overactivity of immune-competent cells can lead to immune infertility, a situation in which a woman’s immune system attacks her own reproductive cells, making it impossible to conceive or maintain a pregnancy. Since the prominent role of the inflammatory response in infertility, including KIR receptors and NK cells, has been postulated, the process of antigen presentation involving major histocompatibility complex (MHC) molecules (HLA) appears to be crucial for a successful pregnancy. Proper interactions between KIR receptors on female uNK cells and HLA class I molecules, with a predominant role for HLA-C, found on the surface of germ cells, are strategically important during embryo implantation. In addition, maintaining a functional balance between activating and inhibitory KIR receptors is essential for proper placenta formation and embryo implantation in the uterus. A disruption of this balance can lead to complications during pregnancy. The discovery of links between KIR and HLA-C has provided valuable information about the complexity of maternal–fetal immune interactions that determine the success of a pregnancy. The great diversity of maternal KIR and fetal HLA-C ligands is associated with the occurrence of KIR/HLA-C combinations that are more or less favorable for reproductive success.

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“…Regarding more Specifically, different alleles of the HLA-B gene have been associated with autoimmune diseases (such as HLA-B27 and its relationship with psoriatic arthritis and In the reproductive field, the HLA antigens have been demonstrated to be crucial for the embryo-maternal tolerance and the achievement of a successful pregnancy (Chattopadhyay et al, 2014;Tersigni et al, 2020). For instance, some molecules as the high polymorphic HLA-C participate in the innate immune system by serving as a ligand for the inhibitory killer cell immunoglobulin-like receptors (KIRs) present on natural killer (NK) cells (Leone et al, 2013;Wilczyńska et al, 2020). HLA-C (along with the HLA-E, G and F ones) from both maternal and paternal origin is highly expressed by the extravillous trophoblasts invading the uterine tissues.…”

Section: Hla-b Genementioning

confidence: 99%

“…A recent study has shown that women affected with MS had lower live birth rates (LBR) compared to unaffected women (irrespective of their infertility diagnosis or treatment) (Houtchens et al, 2020). This statistically significant difference in LBRs was more evident in women in early (Bauer-Mehren et al, 2011;Profaizer and Eckels, 2012;Leone et al, 2013;Chattopadhyay et al, 2014;Mosaad, 2015;Pinero et al, 20152015;Robinson et al, 2015;Piñero et al, 2017;Wieczorek et al, 2017;Jongsma et al, 2019;Piñero et al, 2020;Tersigni et al, 2020;Wilczyńska et al, 2020) and middle (Emmery et al, 2016;Nielsen et al, 2017;Agius et al, 2018;Papúchová et al, 2019) childbearing years. The difference between women with and without MS disappeared after receiving infertility treatments, thus highlighting the importance of information regarding the efficacy of infertility treatments in women with autoimmune diseases (Houtchens et al, 2020).…”

Section: Experimental Autoimmune Encephalomyelitismentioning

confidence: 99%

Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons to be Discovered

et al. 2022

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Human hypofertility and infertility are two worldwide conditions experiencing nowadays an alarming increase due to a complex ensemble of events. The immune system has been suggested as one of the responsible for some of the etiopathogenic mechanisms involved in these conditions. To shed some light into the strong correlation between the reproductive and immune system, as can be inferred by the several and valuable manuscripts published to date, here we built a network using a useful bioinformatic tool (DisGeNET), in which the key genes involved in the sperm-oviduct interaction were linked. This constitutes an important event related with Human fertility since this interaction, and specially the spermatozoa, represents a not-self entity immunotolerated by the female. As a result, we discovered that some proteins involved in the sperm-oviduct interaction are implicated in several immune system diseases while, at the same time, some immune system diseases could interfere by using different pathways with the reproduction process. The data presented here could be of great importance to understand the involvement of the immune system in fertility reduction in Humans, setting the basis for potential immune therapeutic tools in the near future.

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KIR and HLA-C genes in male infertility

Cited by 6 publications

References 44 publications

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure

Immunological Aspects of Infertility—The Role of KIR Receptors and HLA-C Antigen

Human Immune System Diseasome Networks and Female Oviductal Microenvironment: New Horizons to be Discovered

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