The association between killer-cell immunoglobulin-like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

Brochot, Étienne; Desoutter, Judith; Presne, Claire; Araujo, Isabelle De; Flahaut, Gauthier; Castelain, Sandrine; Westeel, Pierre-François; Choukroun, Gabriel; Guillaume, Nicolas

doi:10.1111/tri.12820

Cited by 10 publications

(6 citation statements)

References 15 publications

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“…An allogeneic recognition system consisting of KIR and human leukocyte antigen C (HLA-C) can participate in human immune response under the regulation of NK cells [35]. A number of studies have shown that KIRs are significantly associated with transplant rejection, mainly related to their immune processes and associated with a variety of immune diseases, such as kidney transplantation [36,37], ankylosing spondylitis [38], and psoriatic [39,40]. Previous studies have shown that women with recurrent spontaneous abortion lack inhibitory KIRs (2DL1, 2DL2, and 2DL3) and cannot inhibit the killing activity of NK cells, leading to miscarriage [41].…”

Section: Discussionmentioning

confidence: 99%

Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss

Hao

et al. 2020

Bioscience Reports

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At present, the etiology and pathogenesis of recurrent early pregnancy loss (REPL) are not completely clear. Therefore, identifying the underlying diagnostic and prognostic biomarkers of REPL can provide new ideas for the diagnosis and treatment of REPL. The chip data of REPL (GSE63901) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module for studying the relationship between gene modules and clinical features. In addition, functional analysis of hub genes in modules of interest was performed. A total of 23 co-expression modules were identified, two of which were most significantly associated with three clinical features. The MEbrown module was positively correlated with cyclin E level and the out-of-phase trait while the MEred module was positively correlated with the effect of progesterone. We identified 17 hub genes in the MEred module. The functional enrichment analysis indicated that such hub genes were mainly involved in pathways related to cellular defense response and natural killer (NK) cell-mediated cytotoxicity. In the MEbrown module, we identified 19 hub genes, which were mainly enriched in cell adhesion molecule production, regulation of cellular response to growth factor stimulus, epithelial cell proliferation, and transforming growth factor-β (TGF-β) signaling pathway. In addition, the hub genes were validated by using other datasets and three true hub genes were finally obtained, namely DOCK2 for the MEred module, and TRMT44 and ERVMER34-1 for the MEbrown module. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of REPL.

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Section: Discussionmentioning

confidence: 99%

Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss

Hao

et al. 2020

Bioscience Reports

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“…The HLA molecules interact with KIRs so that HLA molecules act as ligands and KIRs on the NK cell surface act as receptors (Brochot et al 2016). The degree of the contact between KIRs and HLA molecules controls whether activating or inhibitory signals are transmitted, which determines NK cell function (Tuttolomondo et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Determining the relevance of HLA/KIR matching/mismatching on kidney and liver transplantation rejection: A meta-analysis

Batuan

CAJAYON

et al. 2021

Nusantara Biosci

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Abstract. Batuan B, Cajayon CJ, Castro BA, Austria ML, Co DN, Ebreo SK, Clemente B, Tiongco RE. 2021. Determining the relevance of HLA/KIR matching/mismatching on kidney and liver transplantation rejection: A meta-analysis. Nusantara Bioscience 13: 211-218. The kidney and liver are solid organs commonly transplanted nowadays. However, there are cases wherein graft rejection occurs due to foreign Human Leukocyte Antigen (HLA) proteins. Furthermore, the function of Natural Killer (NK) cells and their receptors in solid organ transplantation is not yet fully elucidated. This study aims to determine the relevance of matching HLA/Killer cell Immunoglobulin-like Receptors (KIR) with kidney and liver transplantation outcomes. Articles were screened according to the inclusion and exclusion criteria provided, which garnered eight definitive studies. Next, data were tabulated using a standardized extraction form. A meta-analysis was conducted to formulate conclusions regarding significance of HLA/KIR matching and mismatching in kidney and liver transplantations. Fixed- and random-effects models were utilized to compute and establish 95% CI and pooled ORs wherein a p-value of less than 0.05 is considered significant. A combination of Chi-square based Q test and I2 statistics were used to identify heterogeneity, which was resolved with a funnel plot. In this meta-analysis, only the HLA-Bw4/KIR3DL1 combination was found significant to lower the risk of allograft rejection (OR=0.73; PA=0.009; PH=0.42). Other combinations which include HLA-C1 and KIR2DL2/3, HLA-C1 and KIR2DS2/3, HLA-C2 and KIR2DL1/DS2, and HLA-Bw4/KIR3DS1 were found to be insignificant; hence, these do not influence the allograft rejections. In conclusion, the role of HLA/KIR combinations on solid organ transplantation rejection is only significant in HLA-Bw4/KIR3DL1 interaction which is correlated with decreased odds of allograft rejection. Factors including KIR allele variations, insufficient data and journals related to the topic, and unestablished association of HLA/KIR in other organ transplantations affected the results of this meta-analysis; thus, these are recommended to be considered in future studies.

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“…It is not clear which biological mechanism is underlying these findings for HCMV seronegative patients at the time of transplantation and whether the lack of T or NK cell memory in this specific group in combination with immunosuppression of T cell responses during the initial stage of infection plays a role. A protective role for KIR B haplotypes has also been observed for Varicella zoster (78) and BK virus (79) though two other studies did not find a significant impact of KIR haplotypes on BK virus (78,80). The impact of KIR repertoires on other viral infections is not very well studied.…”

Section: Impact Of Kir-hla Class I Interaction On Kidney Transplantation Outcomementioning

confidence: 99%

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

et al. 2021

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Natural killer (NK) cells are innate lymphocytes that can kill diseased- or virally-infected cells, mediate antibody dependent cytotoxicity and produce type I immune-associated cytokines upon activation. NK cells also contribute to the allo-immune response upon kidney transplantation either by promoting allograft rejection through lysis of cells of the transplanted organ or by promoting alloreactive T cells. In addition, they protect against viral infections upon transplantation which may be especially relevant in patients receiving high dose immune suppression. NK cell activation is tightly regulated through the integrated balance of signaling via inhibitory- and activating receptors. HLA class I molecules are critical regulators of NK cell activation through the interaction with inhibitory- as well as activating NK cell receptors, hence, HLA molecules act as critical immune checkpoints for NK cells. In the current review, we evaluate how NK cell alloreactivity and anti-viral immunity are regulated by NK cell receptors belonging to the KIR family and interacting with classical HLA class I molecules, or by NKG2A/C and LILRB1/KIR2DL4 engaging non-classical HLA-E or -G. In addition, we provide an overview of the methods to determine genetic variation in these receptors and their HLA ligands.

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The association between killer-cell immunoglobulin-like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

Cited by 10 publications

References 15 publications

Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss

Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss

Determining the relevance of HLA/KIR matching/mismatching on kidney and liver transplantation rejection: A meta-analysis

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

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