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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/28814524/mutation-of-the-putative-immunosuppressive-domain-of-the-retroviral-envelope-glycoprotein-compromises-infectivity
#1
Urszula Eksmond, Bryony Jenkins, Julia Merkenschlager, Walther Mothes, Jonathan P Stoye, George Kassiotis
The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#2
REVIEW
Anuradha Ratna, Pranoti Mandrekar
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms...
August 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28780426/characterization-of-oseltamivir-resistant-influenza-virus-populations-in-immunosuppressed-patients-using-digital-droplet-pcr-comparison-with-qpcr-and-next-generation-sequencing-analysis
#3
Maxime Pichon, Alexandre Gaymard, Laurence Josset, Martine Valette, Gilles Millat, Bruno Lina, Vanessa Escuret
INTRODUCTION: The H275Y substitution in neuraminidase (NA) confers oseltamivir-resistance in A(H1N1) influenza viruses (IV). Droplet digital PCR (ddPCR) is a new technique to explore single nucleotide polymorphisms. The aim of this study was to compare the performances of reverse transcriptase (RT)-ddPCR, RT-qPCR and next generation sequencing (NGS). We also analyzed the proportions of H275Y-NA substitution for two immunosuppressed patients with sustained shedding of A(H1N1)pdm09 IV. METHODS: RT-qPCR was performed using the ABI7500 platform...
August 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28756234/anti-tumor-necrosis-factor-with-a-glyco-engineered-fc-region-has-increased-efficacy-in-mice-with-colitis
#4
Felicia M Bloemendaal, Alon D Levin, Manon E Wildenberg, Pim J Koelink, Bradford L McRae, Jochen Salfeld, Jenifer Lum, Marijn van der Neut Kolfschoten, Jill W Claassens, Remco Visser, Arthur Bentlage, Geert R A M D'Haens, J Sjef Verbeek, Gestur Vidarsson, Gijs R van den Brink
BACKGROUND & AIMS: Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease (IBD), complete mucosal healing occurs in less than 50% of patients. The Fc region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We examined the interaction between the anti-TNF Fc region and Fcγ receptors (FcγR), and whether the absence of the Fc core fucose (which increases binding to FcγRIIIa) increases the efficacy of anti-TNF in mice with colitis...
July 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28736028/association-between-tacrolimus-pharmacokinetics-and-cytochrome-p450-3a5-and-multidrug-resistance-protein-1-exon-21-polymorphisms
#5
M Soda, M Fujitani, R Michiuchi, A Shibayama, K Kanamori, S Yoshikuni, Y Ohno, T Tsuchiya, A Suzuki, K Horie, T Deguchi, Y Itoh, K Kitaichi
BACKGROUND: Individual differences in the pharmacokinetics (PK) of tacrolimus (TAC), an immunosuppressive drug, are reportedly associated with single-nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP) 3A5 and multidrug resistance protein 1 (MDR1). We determined the effect of SNPs in CYP3A5 and MDR1 exons 21 and 26 on TAC PK parameters. METHODS: Thirty-eight Japanese patients who underwent renal transplantation were genotyped for CYP3A5 and exons 21 and 26 of MDR1 with the use of polymerase chain reaction-restriction fragment length polymorphism analysis...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28735350/inflammatory-joint-disorders-and-neutrophilic-dermatoses-a-comprehensive-review
#6
REVIEW
Massimo Cugno, Roberta Gualtierotti, Pier Luigi Meroni, Angelo Valerio Marzano
Rheumatoid arthritis and spondyloarthritis are inflammatory joint disorders with an autoimmune pathogenesis and systemic involvement. The skin is one of the most frequently affected extraarticular sites with a number of manifestations or distinct diseases, including common conditions, such as rheumatoid nodules and psoriasis, and rare diseases like neutrophilic dermatoses. The latter are clinically characterised by polymorphic lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers, and histologically by neutrophil-rich inflammatory infiltrates...
July 22, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28729211/insight-into-immunocytes-infiltrations-in-polymorphous-light-eruption
#7
REVIEW
Dongyun Lei, Wenjuan Wu, Li Yang, Yan Li, Jiaqi Feng, Lechun Lyu, Li He
Polymorphous light eruption (PLE) which is one of the most common photodermatoses has been demonstrated to be immune-mediated disorder. Resistance to UV-induced immunosuppression resulting from differential immune cells infiltration and cytokines secretion has been highlighted in the pathogenesis of PLE. In this study, we reviewed differential patterns of immune cells infiltrations and cytokines secretion that may contribute to PLE occurrence and development.
July 17, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28717926/clinical-evaluation-of-modified-release-and-immediate-release-tacrolimus-formulations
#8
Simon Tremblay, Rita R Alloway
The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index...
July 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28706918/the-respiratory-microbiome-in-idiopathic-pulmonary-fibrosis
#9
REVIEW
Richard J Hewitt, Philip L Molyneaux
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease of unknown cause. Current evidence suggests that it arises in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. Overt respiratory infection and immunosuppression carry a high mortality, while polymorphisms in genes related to epithelial integrity and host defence predispose to IPF. Recent advances in sequencing technologies have allowed the use of molecular microbial technologies to characterise the respiratory microbiota in patients with IPF...
June 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28704257/the-combination-of-cyp3a4-22-and-cyp3a5-3-single-nucleotide-polymorphisms-determines-tacrolimus-dose-requirement-after-kidney-transplantation
#10
Nuria Lloberas, Laure Elens, Ines Llaudó, Ariadna Padullés, Teun van Gelder, Dennis A Hesselink, Helena Colom, Franc Andreu, Joan Torras, Oriol Bestard, Josep M Cruzado, Salvador Gil-Vernet, Ron van Schaik, Josep M Grinyó
INTRODUCTION: Tacrolimus (Tac) has a narrow therapeutic window and shows large between-patient pharmacokinetic variability. As a result, over-immunosuppression and under-immunosuppression are frequently encountered in daily clinical practice. Unraveling the impact of genetic polymorphisms on Tac pharmacokinetics may help to refine therapy. In this study, the associations of single-nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes (CYP3A) with Tac pharmacokinetics were investigated in renal transplant recipients...
September 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28700521/effect-of-cyp3a4-and-cyp3a5-genetic-polymorphisms-on-the-pharmacokinetics-of-sirolimus-in-healthy-chinese-volunteers
#11
Jing Zhang, Ying Dai, Zhihong Liu, Minxin Zhang, Chen Li, Dingxiong Chen, Hongtao Song
BACKGROUND: Sirolimus is a promising immunosuppressive drug for preventing the rejection of organ transplants. However, inter-individual variability in sirolimus pharmacokinetics causes adverse drug reactions, compromising therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. METHODS: Thirty-one healthy Chinese volunteers were included in this study...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28673452/circulating-complement-factor-h-related-proteins-1%C3%A2-and-5-correlate-with-disease-activity-in-iga-nephropathy
#12
Nicholas R Medjeral-Thomas, Hannah J Lomax-Browne, Hannah Beckwith, Michelle Willicombe, Adam G McLean, Paul Brookes, Charles D Pusey, Mario Falchi, H Terence Cook, Matthew C Pickering
IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation...
June 30, 2017: Kidney International
https://www.readbyqxmd.com/read/28646274/population-pharmacokinetic-modeling-of-diltiazem-in-chinese-renal-transplant-recipients
#13
Xiao-Feng Guan, Dai-Yang Li, Wen-Jun Yin, Jun-Jie Ding, Ling-Yun Zhou, Jiang-Lin Wang, Rong-Rong Ma, Xiao-Cong Zuo
BACKGROUND AND OBJECTIVES: Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study...
June 23, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28642710/tacrolimus-updated-guidelines-through-poppk-modeling-how-to-benefit-more-from-cyp3a-pre-emptive-genotyping-prior-to-kidney-transplantation
#14
Jean-Baptiste Woillard, Michel Mourad, Michael Neely, Arnaud Capron, Ron H van Schaik, Teun van Gelder, Nuria Lloberas, Dennis A Hesselink, Pierre Marquet, Vincent Haufroid, Laure Elens
Tacrolimus (Tac) is a profoundly effective immunosuppressant that reduces the risk of rejection after solid organ transplantation. However, its use is hampered by its narrow therapeutic window along with its highly variable pharmacological (pharmacokinetic [PK] and pharmacodynamic [PD]) profile. Part of this variability is explained by genetic polymorphisms affecting the metabolic pathway. The integration of CYP3A4 and CY3A5 genotype in tacrolimus population-based PK (PopPK) modeling approaches has been proven to accurately predict the dose requirement to reach the therapeutic window...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28628558/genetics-of-pleiotropic-effects-of-dexamethasone
#15
Laura B Ramsey, Stan Pounds, Cheng Cheng, Xueyuan Cao, Wenjian Yang, Colton Smith, Seth E Karol, Chengcheng Liu, John C Panetta, Hiroto Inaba, Jeffrey E Rubnitz, Monika L Metzger, Raul C Ribeiro, John T Sandlund, Sima Jeha, Ching-Hon Pui, William E Evans, Mary V Relling
OBJECTIVES: Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia...
August 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28628343/chronic-herpetic-retinitis-clinical-features-and-long-term-outcomes
#16
Soufiane Souissi, Christine Fardeau, Hoang Mai Le, Flore Rozenberg, Bahram Bodaghi, Phuc Le Hoang
INTRODUCTION: Chronic uveitis treated with immunosuppressive agents may have unfavorable outcomes due to delays in diagnosis. The aim of this study was to review initial data from clinical and ocular assessments and patient outcomes following specific treatments for atypical herpes virus ocular infections. METHODS: The records of four consecutive patients with recurrent uveitis for at least five years treated in our department between 2001 and 2016 were retrospectively reviewed...
June 19, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#17
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND & AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28614360/comparative-genomics-of-cryptococcus-neoformans-var-grubii-associated-with-meningitis-in-hiv-infected-and-uninfected-patients-in-vietnam
#18
COMPARATIVE STUDY
Jeremy N Day, Seet Qihui, Lam Tuan Thanh, Phan Hai Trieu, Anh Duong Van, Nha Hoang Thu, Tran Thi Hong Chau, Nguyen P H Lan, Nguyen Van Vinh Chau, Philip M Ashton, Guy E Thwaites, Maciej F Boni, Marcel Wolbers, Niranjan Nagarajan, Patrick B O Tan, Stephen Baker
The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28588572/positively-selected-sites-at-hcmv-gb-furin-processing-region-and-their-effects-in-cleavage-efficiency
#19
Lucas M Stangherlin, Felipe N de Paula, Marcelo Y Icimoto, Leonardo G P Ruiz, Maurício L Nogueira, Antônio S K Braz, Luiz Juliano, Maria C C da Silva
Human cytomegalovirus is a ubiquitous infectious agent that affects mainly immunosuppressed, fetuses, and newborns. The virus has several polymorphic regions, in particular in the envelope glycoproteins. The UL55 gene encodes the glycoprotein B that has a variable region, containing a furin cleavage site and according to the variability different genotypes are characterized. Here we investigated variability and existence of selective pressure on the UL55 variable region containing the furin cleavage site in 213 clinical sequences from patients worldwide...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28567557/c-reactive-protein-1444ct-rs1130864-genetic-polymorphism-is-associated-with-the-susceptibility-to-systemic-lupus-erythematosus-and-c-reactive-protein-levels
#20
Francieli Delongui, Marcell Allyson Batisti Lozovoy, Tatiana Mayiumi Veiga Iriyoda, Neide Tomimura Costa, Nicole Perugini Stadtlober, Daniela Frizon Alfieri, Tamires Flauzino, Isaias Dichi, Andréa Name Colado Simão, Edna Maria Vissoci Reiche
The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls...
August 2017: Clinical Rheumatology
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