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R&D IRG

As part of the new proposals for molecular diagnostics and clinical researchof the section, the analysis HLA-G 3'UTR polymorphic variants and KIR gene polymorphisms is region of the HLA-G gene deserves a special mentionand polymorphic variants of KIR genes for the study of predispositionof couple to spontaneous abortion, implantation failure and idiopathic infertility

 

In collaboration with:

IRG X MERCK
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Peer review 2024/2025

(under peer review)

Click on the images to read and download the research on the role of the KIR genotype

in women with unknown infertility and implantation failures in assisted reproductive technology

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The role of KIR HLA-C genes in ART setups

The role of KIR genes in PMA setups
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What is the purpose of the KIR HLA-C test ?

Early embryonic-fetal loss is a major cause of primary infertility and reproductive failure.
In recent years, maternal immunological mismodulation of fetal antigen status (semiallogenic allograft) has emerged as an important etiogenetic factor, with increasing clinical and experimental evidence.
Defects in functional interaction (crosstalk) between extravillous trophoblastic cells (EVT) and decidual Natural Killer cells are thought to be responsible for a broad spectrum of pregnancy-specific disorders, such as.

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Under normal physiological conditions, surface antigens expressed by Natural Killer cells (killer immunoglobulin-like receptors) interact with HLA-C type C1/C2 receptors expressed by placental cells to promote trophoblastic invasion and vascular remodeling.
The secretion of specific pro-angiogenic factors, chemokines, and cytokines is modulated by the "particular" interaction between specific KIR/HLA-C epitopes.


The two different cell types, of maternal (uNK) and fetal (trophoblast) origin, have the potential to trigger different biomolecular responses depending on the expressed antigenic repertoire. Based on a purely functional criterion (prevalence or otherwise of uNK-mediated cytotoxic and pro-angiogenic activity), the numerous KIR gene variants have been classified into two categories: activators and inhibitors.


Considering that many KIR loci polymorphisms tend to co-occur (linkage disequilibrium), it was possible to derive a specific genetic haplotype for each patient:
KIR A if only inhibitory genotypes are present, and KIR B if activator genotypes are also present according to molecular analysis.


More recent studies conducted on embryo biopsies (PGS/PGD) recruiting a cohort of patients with a history of miscarriage and implantation failure show that certain maternal-fetal antigen combinations, such as KIR A/c2 c2 (paternal c2 contribution) and KIR B/c1c1, confer a significantly increased risk of early or early fetal loss.
These observations suggest implementing genetic profiling for the KIR and c1/c2 haplotypes in clinical practice in couples undergoing assisted reproduction protocols with a clinical history of infertility and a history of early fetal loss, and in cases of reproductive cell donation (oocytes and sperm).


EDTA sample
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