Changes of NK cell subsets with time post-transplant in peripheral blood of renal transplant recipients

Zhu, Li; Aly, Mostafa; Wang, Haihao; Karakizlis, Hristos; Weimer, Rolf; Morath, Christian; Kuon, Ruben; Tóth, Bettina; Ekpoom, Naruemol; Opelz, Gerhard; Daniel, Volker

doi:10.1016/j.trim.2018.04.005

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…Since HLA-C alleles are inhibitory ligands protecting cellular targets from NK cell lysis, antibody responses against C1/NK2 and C2/NK1 alleles may play an important role in NK cell function in the transplantation context. Although the presence of C1 and C2 alleles is part of algorithms used for better allocation of bone marrow donors, the role of NK cells in organ transplantation is not studied so much (35,36). However, very recent studies underlined a prominent role of NK1 versus NK2 responses for graft tolerance (32).…”

Section: Discussionmentioning

confidence: 99%

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

et al. 2021

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Detection of alloreactive anti-HLA antibodies is a frequent and mandatory test before and after organ transplantation to determine the antigenic targets of the antibodies. Nowadays, this test involves the measurement of fluorescent signals generated through antibody–antigen reactions on multi-beads flow cytometers. In this study, in a cohort of 1,066 patients from one country, anti-HLA class I responses were analyzed on a panel of 98 different antigens. Knowing that the immune system responds typically to “shared” antigenic targets, we studied the clustering patterns of antibody responses against HLA class I antigens without any a priori hypothesis, applying two unsupervised machine learning approaches. At first, the principal component analysis (PCA) projections of intra-locus specific responses showed that anti-HLA-A and anti-HLA-C were the most distantly projected responses in the population with the anti-HLA-B responses to be projected between them. When PCA was applied on the responses against antigens belonging to a single locus, some already known groupings were confirmed while several new cross-reactive patterns of alloreactivity were detected. Anti-HLA-A responses projected through PCA suggested that three cross-reactive groups accounted for about 70% of the variance observed in the population, while anti-HLA-B responses were mainly characterized by a distinction between previously described Bw4 and Bw6 cross-reactive groups followed by several yet undocumented or poorly described ones. Furthermore, anti-HLA-C responses could be explained by two major cross-reactive groups completely overlapping with previously described C1 and C2 allelic groups. A second feature-based analysis of all antigenic specificities, projected as a dendrogram, generated a robust measure of allelic antigenic distances depicting bead-array defined cross reactive groups. Finally, amino acid combinations explaining major population specific cross-reactive groups were described. The interpretation of the results was based on the current knowledge of the antigenic targets of the antibodies as they have been characterized either experimentally or computationally and appear at the HLA epitope registry.

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Section: Discussionmentioning

confidence: 99%

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

et al. 2021

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“…Evidence from previous transplant association studies suggests that the genes ACE, IL4R , and AGTR1 were implicated in acute rejection, and SNPs from ACE , including our top SNP rs4363, were found to be associated with sudden cardiac death in kidney transplant (Moe et al, 2018). Additionally, gene expression studies found that expression levels of AGTR1 tended to be increased for heart transplant recipients with recurrent rejection episodes, and expression levels of IL4R were increased in natural killer cells after kidney transplant (Yamani et al, 2006; Zhu et al, 2018). While these genes were not directly implicated in liver transplant outcomes, the fact that they were found to be significant in other transplant scenarios is encouraging.…”

Section: Discussionmentioning

confidence: 99%

Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes

Arthur

Guan

Loza

et al. 2020

Genetic Epidemiology

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Genetic matching between transplant donor and recipient pairs has traditionally focused on the human leukocyte antigen (HLA) regions of the genome, but recent studies suggest that matching for non‐HLA regions may be important as well. We assess four genetic matching scores for use in association analyses of transplant outcomes. These scores describe genetic ancestry distance using identity‐by‐state, or genetic incompatibility or mismatch of the two genomes and therefore may reflect different underlying biological mechanisms for donor and recipient genes to influence transplant outcomes. Our simulation studies show that jointly testing these scores with the recipient genotype is a powerful method for preliminary screening and discovery of transplant outcome related single nucleotide polymorphisms (SNPs) and gene regions. Following these joint tests with marginal testing of the recipient genotype and matching score separately can lead to further understanding of the biological mechanisms behind transplant outcomes. In addition, we present results of a liver transplant data analysis that shows joint testing can detect SNPs significantly associated with acute rejection in liver transplant.

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“…NK-клетки и клетки трофобласта могут синтезировать противовоспалительный цитокин IL-10 [21,117] и его рецептор IL-10R [118,169]. IL-10 может усиливать цитотоксический потенциал естественных киллеров, стимулировать пролиферацию клеток, а также индуцировать синтез IFNγ [14].…”

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Decidual natural killer cells and trophoblast cells: cellular, humoral and molecular mechanisms of interaction

et al. 2022

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Natural killer cells (NK cells) represent a group of lymphocytes of innate immunity. In addition to NK cells of peripheral blood, tissue-resident populations are described. NK cells of the decidual envelope (decidual NK cells) represent one of the local NK cell populations. Decidual NK cells differ in phenotype and function from peripheral blood NK cells. These cells have, mainly, regulatory functions. At the same time they retain the ability to perform cytotoxic effects. In the uterus, NK cells are located closely to the cells of fetal origin, i.e., trophoblast cells, which differentiate from the outer layer of the invading blastocyst. The purpose of the review article was to analyze the literature data on the studies of the molecular interactions between NK cells and trophoblast cells, as well as potential means of regulating these interactions. The review presents currently available data on receptor-mediated effects (due to adhesion molecules and cytotoxic receptors) and distant interactions (involving cytokines, chemokines and growth factors secreted by the both cell types) between NK population and trophoblast cells. The receptors regulating contacts of NK cells and trophoblast cells with extracellular matrix are also considered. The review provides information on activation of signaling pathways in NK cells and trophoblast cells resulting from their interaction with each other and components of the extracellular matrix. Currently, the molecular mechanisms regulating the NK cell functions and their interaction with trophoblast cells have not been studied sufficiently. The authors attempted to consider molecular regulation of the functional activity of NK cells mediated by the molecular complex of RNA polymerase II. We also describe participation of cyclin-dependent CDK8/19 kinases which comprise a part of the mediator complex which provides functioning of immune cells. The data on the participation of CDK8/19 in regulation of intracellular signaling pathways, as well as influence of CDK8/19 on the NK cell functions, are considered. Summarizing the data presented in the literature, one may emphasize that there is an extensive mutual influence of NK cells and trophoblast cells in decidual lining of uterus during pregnancy, thus leading to a changes in phenotype and functions of these cells. Experimental studies are required on the contribution of molecular mechanisms involved in transcription and translation processes to the biology of NK cells, and their role in maintaining interactions between NK cells and trophoblast cells, including the pathways involving CDK8/19.

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Changes of NK cell subsets with time post-transplant in peripheral blood of renal transplant recipients

Cited by 11 publications

References 27 publications

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes

Decidual natural killer cells and trophoblast cells: cellular, humoral and molecular mechanisms of interaction

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