Novel <i>KIR</i> genotypes and gene copy number variations in northeastern Thais

Chaisri, Suwit; Traherne, James A.; Jayaraman, Jyothi; Romphruk, Amornrat; Trowsdale, John

doi:10.1111/imm.12847

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…Natural killer cells (NK) play a crucial role in the innate defense against tumors and viral infections also contributing to the immune response during chronic HCV infections [4][5][6]. NK cells activity is regulated by stimulatory and inhibitory NK receptors (NKRs) which consist mainly of inhibitory killer Ig-like receptors (KIRs) [7].…”

Section: Introductionmentioning

confidence: 99%

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

Ursu

Calenic

Diculescu

et al. 2020

JGLD

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Background and Aims: The role of natural killer (NK) cells in the defense against hepatitis C virus (HCV) infection involve both innate and adaptive immunity. NK cells express a large panel of inhibitory and activating receptors who bind human leukocyte antigen (HLA) class I receptors. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic of these receptors being encoded by genes distributed differently in unrelated individuals. The aim of this study was to look at the immune response in chronic HCV patients by assessing NK-KIR genes and their corresponding HLA ligands. Methods: We genotyped 127 chronically HCV-infected patients and 130 non-infected healthy individuals for both KIR genes and their HLA ligands. The HLA-A, HLA-B, HLA-C genotypes were analyzed using polymerase chain reaction high-resolution typing. Results: KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3, KIR2DP1, KIR3DP1 genes were significantly increased in the HCV group compared to healthy individual. Analysis of various HLA haplotypes revealed different HLA alleles associated with increased susceptibility to HCV infection. Thus, HLA A*23:01 was more frequent in the patients’ group than in the controls (p=0.030). At the same time HLA B*44:02 and C*04:02 were significantly elevated in HCV-positive patients (p=0.008 and respectively p= 0.007). Conclusions: These results suggest that the expression of KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3 genes and the association with HLA alleles such as HLA A*23:01, B*44:02, C*04:02 may increase the patient susceptibility to chronic HCV infection.

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Section: Introductionmentioning

confidence: 99%

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

Ursu

Calenic

Diculescu

et al. 2020

JGLD

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“…It is well established that inhibitory killer Ig‐like receptors (KIRs) are the most polymorphic NK receptors (Mozer‐Lisewska et al., 2016). They can bind specific ligands and exhibit either a stimulatory or an inhibitory effect on NK cells (Chaisri et al., 2018). KIR genes comprise six genes with activating effects (2DS1, 2DS2, 2DS3, 2DS4, 2DS5 and 3DS1), seven genes encoding inhibitory KIR (2DL1, 2DL2, 2DL3, 2DL5, 2DL5null, 3DL1 and 3DL2) and two pseudogenes (2DP1 and 3DP1).…”

Section: Introductionmentioning

confidence: 99%

“…It is well established that inhibitory killer Ig-like receptors (KIRs) are the most polymorphic NK receptors (Mozer-Lisewska et al, 2016). They can bind specific ligands and exhibit either a stimulatory or an inhibitory effect on NK cells (Chaisri et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Clinical and histopathological changes in different KIR gene profiles in chronic HCV Romanian patients

Ursu

Calenic

Diculescu

et al. 2020

Int J Immunogenetics

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Hepatitis C virus (HCV)‐infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin‐like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV‐infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), direct bilirubin (DB), alpha‐fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well‐established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence‐specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA‐C*12:02 and HLA‐A3 and HLA‐A11 were positively associated with the F3‐F4 fibrosis group (p = .026; OR = 8.717, CI = 1.040–73.077; respectively, p = .047; OR = 2.187; 95% CI = 1.066–4.486). KIR2DL2‐positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2‐negative patients (p = .013, respectively, p = .028). KIR2DL2/KIR2DL2‐C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2‐C1‐positive patients when compared to KIR2DS2‐C1‐negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV‐infected patients. These connections should be taken into account when considering disease development and treatment.

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“…Previous analyses showed that there are A and B haplotypes of the KIR gene organization. More than 50 distinct KIR haplotypes have been identified [ 10 , 11 , 12 ]. The genomic organization of KIR haplotypes contains four framework genes— KIR3DL3 , 3DP1 , 2DL4 and 3DL2 —which are present on all human KIR haplotypes.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Multiplex Real-Time Reverse Transcriptase–Polymerase Chain Reaction with Fluorescent Probe Detection of Killer Immunoglobulin-Like Receptors, KIR2DL4/3DL3

et al. 2020

Self Cite

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(1) Background: KIR2DL4/KIR3DL3 are the framework genes present in all KIR haplotypes, with unique expression patterns being present only in women and CD56bright NK cells. KIR genes have a high degree of DNA sequence identity. Consequently, they are one of the most challenging genes for molecular detection—especially regarding expressions; (2) Methods: We developed an effective method to determine KIR3DL3/KIR2DL4 expressions based on a multiplex quantitative real-time Reverse transcription polymerase chain reaction (qRT-PCR )with fluorescent probes using NK92; (3) Results: Standardizations of the singleplex KIR2DL4 and KIR3DL3 were performed to evaluate the sensitivity and specificity for further development of the multiplex assay. The limit of detection was at 500 copies each. There was cross-amplification with the presence of related KIR genes at a level of 5 × 107 copies. This is not biologically significant because this high level of KIR expression has not been found in clinical samples. The multiplex assay was reproducible equivalent to its singleplex (KIR2DL4; R2 = 0.995, KIR3DL3; R2 = 0.996, but lower sensitivity of 103 copies). Furthermore, the validation of the developed method on samples of blood donors showed high sensitivity (100%) and specificity (99.9%); (4) Conclusions: The developed method is reliable and highly specific suitable for evaluation of the KIR2DL4/3DL3 mRNA expressions in further applications.

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Novel KIR genotypes and gene copy number variations in northeastern Thais

Cited by 7 publications

References 48 publications

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

Clinical and histopathological changes in different KIR gene profiles in chronic HCV Romanian patients

Quantitative Multiplex Real-Time Reverse Transcriptase–Polymerase Chain Reaction with Fluorescent Probe Detection of Killer Immunoglobulin-Like Receptors, KIR2DL4/3DL3

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