Distribution of killer cell immunoglobulin-like receptors (KIR) and their HLA-C ligands in two Iranian populations

Hiby, Susan E.; Bonab, Maziar Ashrafian; Farrell, Lydia; Single, Richard M.; Balloux, François; Carrington, Mary; Moffett, Ashley

doi:10.1007/s00251-009-0408-5

Cited by 35 publications

(23 citation statements)

References 37 publications

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“…Defaults in trophoblast invasion and/or vascular remodelling are hallmarks of pathological pregnancy, such as pre‐eclampsia. Genetic studies suggested that special combinations of fetal HLA‐C haplotypes and maternal dNK cell inhibitory KIRs increased the likelihood of pre‐eclampsia . In a similar manner, the association of some HLA‐C genotypes and maternal KIRs has been linked to defaults in trophoblast invasion.…”

Section: Functions Of Dnk Cells Under Normal Pregnancy: Mother's Littmentioning

confidence: 98%

The up side of decidual natural killer cells: new developments in immunology of pregnancy

2014

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SummaryEarly phases of human pregnancy are associated with the accumulation of a unique subset of natural killer (NK) cells in the maternal decidua. Decidual NK (dNK) cells that are devoid of cytotoxicity play a pivotal role in successful pregnancy. By secreting large amounts of cytokines/chemokines and angiogenic factors, dNK cells participate in all steps of placentation including trophoblast invasion into the maternal endometrium and vascular remodelling. In this review, we summarize some of dNK cell features and discuss more recent exciting data that challenge the conventional view of these cells. Our new data demonstrate that dNK cells undergo fine tuning or even subvert their classical inhibitory machinery and turn into a real defence force in order to prevent the spread of viruses to fetal tissue. Today it is not clear how these phenotypic and functional adaptations impact cellular cross-talk at the fetal-maternal interface and tissue homeostasis. Ultimately, precise understanding of the molecular mechanisms that govern dNK cell plasticity during congenital human cytomegalovirus infection should lead to the design of more robust strategies to reverse immune escape during viral infection and cancer.Keywords: cytomegalovirus; decidua; natural killer cells; pregnancy.Natural killer (NK) cells are large granular lymphocytes of the innate immune system and represent the first line in the host defence against invading pathogens.1,2 Unlike T cells, NK cells do not express an antigen-specific receptor but rather they express a large repertoire of activating and inhibitory receptors. Mature NK cells recirculate in the blood (pNK) where their number varies anywhere from 5 to 20% of total lymphocytes. Natural killer cells are also present in lymphoid and non-lymphoid tissues including the uterus where they are mainly CD56 bright CD16 neg . 3 Given the fact that these cells are fully armed with cytolytic granules that can cause great harm, their activation is regulated by germline-encoded inhibitory or activating cell surface receptors that recognize self-ligands or pathogen-induced and stress-induced ligands. 4 The net balance between activating and inhibitory signals would determine the outcome of NK cell responses against various threats. Activation of NK cells is inhibited mainly after interaction of inhibitory receptors with MHC class I molecules. However, the loss of MHC class I expression is not sufficient to trigger NK cell responsiveness because additional activating signals are required. 5 The NK cells can eliminate their target through different mechanisms, including direct cell cytotoxicity or cytokine production. Besides their role as effectors of innate immunity, NK cells play a pivotal role in bridging the innate and adaptive arms of the immune system. By secreting large amounts of cytokines and chemokines, NK cells impact dendritic cell maturation 6,7 and antigen-specific adaptive immune responses. 8,9 During pregnancy, a special population of NK cells accumulates within the endometrium, which constit...

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Section: Functions Of Dnk Cells Under Normal Pregnancy: Mother's Littmentioning

confidence: 98%

The up side of decidual natural killer cells: new developments in immunology of pregnancy

2014

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“…A protective association of some activating KIRs of the telomeric B haplotype region, particularly 2DS1 as well as 3DS1, 2DS5, and 2DL5, with RSA was reported in an English Caucasian population composed of 95 RSA cases and 269 controls (Moffett and Colucci, 2015). Moreover, in the same study population, the AA haplotype was found to be positively associated with recurrent miscarriage (Hiby et al, 2010b;Moffett and Colucci, 2015). reported a protective effect of the KIR AA haplotype and inhibitory genes in an Asian Indian population composed of 205 women with a history of RSA and 224 controls belonging to different ethnic groups.…”

Section: Discussionmentioning

confidence: 68%

“…In this study, authors did not consider the 2DL5 gene and failed to amplify the 2DS3 genes in both case and groups (Ay et al, 2019). These conflicting results are a subject of controversy and debate regarding the method of typing and the matching of patients and controls according to ethnic origin as well as exclusion criteria/inclusion in the choice of patients and controls (Faridi and Agrawal, 2009;Hiby et al, 2010b). Indeed, in almost all studies, the patients and controls were not selected according to the same criteria regarding the number of spontaneous abortions in the patient group and the number of pregnancies in the control group.…”

Section: Discussionmentioning

confidence: 81%

Association of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Class I Ligand with Recurrent Abortion in Saudi Women

Mansour

Alkhuriji

Babay

et al. 2020

Genetic Testing and Molecular Biomarkers

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This study was designed to determine whether genetic polymorphisms of the killer immunoglobulin-like receptor (KIR) and human leukocyte antigen class I (HLA-C) genes are associated with recurrent spontaneous abortion (RSA) in Saudi women. Materials and Methods: Sixty-five healthy women with a history of RSA (three or more spontaneous abortions) and 65 healthy controls (with two or more healthy-born children) living in Riyadh were typed for 17 KIR genes and the HLA-C1 and HLA-C2 allotypes using polymerase chain reaction-sequence-specific primer methodology. Results: The frequencies of KIR2DS2 and KIR2DL5A were significantly lower among RSA women compared to healthy controls (odds ratio [OR] = 0.17; p < 0.001; OR = 0.16; p < 0.001, respectively). No association with maternal HLA-C genotypes was observed. Analysis of KIR-HLA-C combinations indicated a protective effect of KIR2DS2 with its cognate HLA-C1 ligand in both homozygote or heterozygote combinations. Conclusion: Our results demonstrate that the KIR genes of the B haplotype may play an important role in ensuring the success of pregnancy.

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“…52 We found that the gene carrier frequencies were very similar to those of published KIR gene carrier frequencies from an English cohort of Caucasoid ethnicity. 54 (Figure 1a). The software was unable to predict possible haplotype pairs for 3% (n=25) of cases.…”

Section: High Accuracy For Identifying Kir Gene Absence/presencementioning

confidence: 99%

In silicotools for accurate HLA and KIR inference from clinical sequencing data empower immunogenetics on individual-patient and population scales

Chen¹,

Madireddi²,

Nagarkar³

et al. 2020

Preprint

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Immunogenetic variation in humans is important in research, clinical diagnosis and increasingly a target for therapeutic intervention. Two highly polymorphic loci play critical roles, namely the human leukocyte antigen (HLA) system, which is the human version of the major histocompatibility complex (MHC), and the Killer-cell immunoglobulin-like receptors (KIR) that are relevant for responses of Natural Killer (NK) cells and some subsets of T cells. Their accurate classification has typically required the use of dedicated biological specimens and a combination of in vitro and in silico efforts. Increased availability of next generation sequencing data has led to the development of ancillary computational solutions. Here, we report an evaluation of recently published algorithms to computationally infer complex immunogenetic variation in the form of HLA alleles and KIR haplotypes from whole-genome or whole-exome sequencing data. For both HLA allele and KIR gene typing, we identified tools that yielded >97% overall accuracy for 4-digit HLA types, and >99% overall accuracy for KIR gene presence, suggesting the readiness of in silico solutions for use in clinical and high-throughput research settings.

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Distribution of killer cell immunoglobulin-like receptors (KIR) and their HLA-C ligands in two Iranian populations

Cited by 35 publications

References 37 publications

The up side of decidual natural killer cells: new developments in immunology of pregnancy

The up side of decidual natural killer cells: new developments in immunology of pregnancy

Association of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Class I Ligand with Recurrent Abortion in Saudi Women

In silicotools for accurate HLA and KIR inference from clinical sequencing data empower immunogenetics on individual-patient and population scales

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