scholarly journals Pharmacogenomics of Antibiotics

2020 ◽  
Vol 21 (17) ◽  
pp. 5975
Author(s):  
Gabriele Stocco ◽  
Marianna Lucafò ◽  
Giuliana Decorti
Keyword(s):  
Adverse Reactions ◽  
Potential Role ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Variable Response ◽  
Metabolizing Enzymes ◽  
Disease Response ◽  
Leukocyte Antigen ◽  
Immune Mediated ◽  
Genes Encoding

Although the introduction of antibiotics in medicine has resulted in one of the most successful events and in a major breakthrough to reduce morbidity and mortality caused by infectious disease, response to these agents is not always predictable, leading to differences in their efficacy, and sometimes to the occurrence of adverse effects. Genetic variability, resulting in differences in the pharmacokinetics and pharmacodynamics of antibiotics, is often involved in the variable response, of particular importance are polymorphisms in genes encoding for drug metabolizing enzymes and membrane transporters. In addition, variations in the human leukocyte antigen (HLA) class I and class II genes have been associated with different immune mediated reactions induced by antibiotics. In recent years, the importance of pharmacogenetics in the personalization of therapies has been recognized in various clinical fields, although not clearly in the context of antibiotic therapy. In this review, we make an overview of antibiotic pharmacogenomics and of its potential role in optimizing drug therapy and reducing adverse reactions.

scholarly journals Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Shih-Chi Su ◽  
Wen-Hung Chung ◽  
Shuen-Iu Hung
Keyword(s):  
Adverse Drug Reactions ◽  
Genetic Variants ◽  
Human Leukocyte ◽  
Clinical Problem ◽  
Drug Reactions ◽  
Metabolizing Enzymes ◽  
Leukocyte Antigen ◽  
Genomic Technologies ◽  
Genes Encoding ◽  
Modern Genomic

Adverse drug reactions (ADRs) are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized.

scholarly journals Immunoinformatic Docking Approach for the Analysis of KIR3DL1/HLA-B Interaction

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Alba Grifoni ◽  
Carla Montesano ◽  
Atanas Patronov ◽  
Vittorio Colizzi ◽  
Massimo Amicosante
Keyword(s):  
Energy Minimization ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Receptor Interaction ◽  
Immune Control ◽  
Immunoglobulin Receptor ◽  
Leukocyte Antigen ◽  
Immune Mediated ◽  
Successful Prediction ◽  
Docking Approach

KIR3DL1 is among the most interesting receptors studied, within the killer immunoglobulin receptor (KIR) family. Human leukocyte antigen (HLA) class I Bw4 epitope inhibits strongly Natural Killer (NK) cell’s activity through interaction with KIR3DL1 receptor, while Bw6 generally does not. This interaction has been indicated to play an important role in the immune control of different viral infectious diseases. However, the structural interaction between the KIR3DL1 receptor and different HLA-B alleles has been scarcely studied. To understand the complexity of KIR3DL1-HLA-B interaction, HLA-B alleles carrying Bw4/Bw6 epitope and KIR3DL1*001 allele in presence of different peptides has been evaluated by using a structural immunoinformatic approach. Different energy minimization force fields (ff) have been tested and NOVA ff enables the successful prediction of ligand-receptor interaction. HLA-B alleles carrying Bw4 epitope present the highest capability of interaction with KIR3DL1*001 compared to the HLA-B alleles presenting Bw6. The presence of the epitope Bw4 determines a conformational change which leads to a stronger interaction between nonpolymorphic arginine at position 79 of HLA-B and KIR3DL1*001 136–142 loop. The data shed new light on the modalities of KIR3DL1 interaction with HLA-B alleles essential for the modulation of NK immune-mediated response.

scholarly journals The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

2020 ◽  
Vol 117 (21) ◽  
pp. 11636-11647 ◽  
Author(s):  
Philippa M. Saunders ◽  
Bruce J. MacLachlan ◽  
Phillip Pymm ◽  
Patricia T. Illing ◽  
Yuanchen Deng ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Peptide Binding ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cell Recognition ◽  
Leukocyte Antigen ◽  
Binding Cleft

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.

scholarly journals Multiple sclerosis: disease modifying therapy and the human leukocyte antigen

2018 ◽  
Vol 76 (10) ◽  
pp. 697-704 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Cláudia Suemi Kamoi Kay ◽  
Rosana Herminia Scola
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Interferon Β ◽  
Leukocyte Antigen ◽  
Specific Subset ◽  
Hla Type ◽  
Disease Modifying

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

scholarly journals Spondyloarthritis and the Human Leukocyte Antigen (HLA)-B*27 Connection

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengappa G. Kavadichanda ◽  
Jie Geng ◽  
Sree Nethra Bulusu ◽  
Vir Singh Negi ◽  
Malini Raghavan
Keyword(s):  
Endoplasmic Reticulum ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Clinical Aspects ◽  
Susceptibility Loci ◽  
New Bone Formation ◽  
High Association ◽  
Leukocyte Antigen ◽  
Heavy Chains

Heritability of Spondyloarthritis (SpA) is highlighted by several familial studies and a high association with the presence of human leukocyte antigen (HLA)-B*27. Though it has been over four decades since the association of HLA-B*27 with SpA was first determined, the pathophysiological roles played by specific HLA-B*27 allotypes are not fully understood. Popular hypotheses include the presentation of arthritogenic peptides, triggering of endoplasmic reticulum (ER) stress by misfolded HLA-B*27, and the interaction between free heavy chains or heavy chain homodimers of HLA-B*27 and immune receptors to drive IL-17 responses. Several non-HLA susceptibility loci have also been identified for SpA, including endoplasmic reticulum aminopeptidases (ERAP) and those related to the IL-23/IL-17 axes. In this review, we summarize clinical aspects of SpA including known characteristics of gut inflammation, enthesitis and new bone formation and the existing models for understanding the association of HLA-B*27 with disease pathogenesis. We also examine newer insights into the biology of HLA class I (HLA-I) proteins and their implications for expanding our understanding of HLA-B*27 contributions to SpA pathogenesis.

scholarly journals High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

BMC Cancer ◽  
2009 ◽  
Vol 9 (1) ◽  
Author(s):  
David Cantú de León ◽  
Delia Pérez-Montiel ◽  
Verónica Villavicencio ◽  
Alejandro García Carranca ◽  
Alejandro Mohar Betancourt ◽  
...  
Keyword(s):  
Sporadic Breast Cancer ◽  
Case Control Study ◽  
Human Leukocyte ◽  
Breast Cancer Case ◽  
Hla Class I ◽  
Case Control ◽  
Cancer Case ◽  
Mexican Mestizo ◽  
Leukocyte Antigen ◽  
Control Study

Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, And Pathology

2018 ◽  
Author(s):  
Walter P Maksymowych
Keyword(s):  
Association Studies ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Population Based ◽  
Cell Phenotype ◽  
Imaging Data ◽  
Leukocyte Antigen ◽  
Seronegative Spondyloarthritis ◽  
Magnetic Resonance Imaging Mri

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI. This review contains 8 figures, 5 tables and 33 references Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis

Characteristics allelic of Human Leukocyte Antigen class I genotype and association with viral load and CD4 cell count in HIV-1 infected patients, Hanoi 2014 – 2016

2021 ◽  
Vol 31 (4) ◽  
pp. 43-50
Author(s):  
Tran Thi Minh Tam ◽  
Nguyen Thuy Linh ◽  
Phan Ha My ◽  
Nguyen Thi Lan Anh
Keyword(s):  
Viral Load ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cd4 Cell Count ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Human Leukocyte Antigen (HLA) class I plays a regulatory role in cellular immune response to HIV-1 infection. The role of HLA alleles in HIV progression via viral load and CD4 cell count is well known. HLA class I is polymorphic and distributed differently by nation. This descriptive cross-sectional study was performed on 303 HIV-1 infected patients in 2014 - 2016, with aims to (i) characterize HLA class I genotype with 4-digit nomenclature and (ii) identify specifc alleles in correlate with CD4 cell counts and HIV viral load. 117 allele genotypes have been identifed, including 28 HLA-A alleles, 54 HLA-B alleles and 35 HLA-C alleles. The results showed that the most prevalent alleles in the population include A*11:01 (30.7%), B*15:02 (15.2%) and C*08:01 (17.1%). The frequency of haplotype created from these alleles is 8.4%. A*02:03, B*46:01 related to gender and ethnicity respectively. In conclusion, the study provided detailed pattern of HLA class I expression in a study population of HIV-1 infected patients and reported for the frst time the associated B*51:01, C*14:02 alleles associated to an increase in CD4 cell counts.

scholarly journals A Unique Regulation Region in the 3′ UTR of HLA-G with a Promising Potential

2020 ◽  
Vol 21 (3) ◽  
pp. 900 ◽  
Author(s):  
Adi Reches ◽  
Orit Berhani ◽  
Ofer Mandelboim
Keyword(s):  
Human Leukocyte Antigen ◽  
Expression Pattern ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Leukocyte Antigen ◽  
Distinct Site ◽  
Human Leukocyte Antigen G ◽  
Classical Human Leukocyte Antigen

Human leukocyte antigen G (HLA-G) is a non-classical human leukocyte antigen (HLA) class I protein that interacts with inhibitory receptors and is commonly overexpressed in various cancers, thereby establishing itself as an inhibitory checkpoint immune ligand. It is also expressed in trophoblast cells during pregnancy and protects the fetus from immune rejection. Despite its crucial role and its intriguing expression pattern, the regulation of HLA-G’s expression is only partially understood. HLA-G’s mRNA is expressed in many tissues but the protein expression is restricted only to the cells mentioned above. Therefore, we suggest that HLA-G is post-transcriptionally regulated. Here, we reveal a distinctive site present only in the 3′ Untranslated region (UTR) of HLA-G, which might explain its unique expression pattern. Consequently, we attempted to find binding factors such as RNA binding proteins (RBPs) and microRNAS (miRs) that regulate HLA-G expression by interacting with this distinct site present in its 3′ UTR. Our research indicates that this site should be further studied in order to reveal its significance.

Sign in / Sign up

Export Citation Format

Share Document