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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/29021921/post-transplant-lymphoproliferative-disorder-ptld-single-institutional-experience-of-141-patients
#1
Rohit Bishnoi, Ravneet Bajwa, Aaron J Franke, William Paul Skelton, Yu Wang, Niraj M Patel, William Birdsall Slayton, Fei Zou, Nam H Dang
BACKGROUND: Post-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world. METHODS: This study was performed at University of Florida which is one of the largest transplant center in South East United States...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28965162/germline-polymorphisms-in-myeloid-associated-genes-are-not-associated-with-survival-in-glioma-patients
#2
Daniel I Jacobs, Yanhong Liu, Konrad Gabrusiewicz, Spiridon Tsavachidis, Georgina N Armstrong, Renke Zhou, Jun Wei, Cristina Ivan, George Calin, Annette M Molinaro, Terri Rice, Paige M Bracci, Helen M Hansen, John K Wiencke, Margaret R Wrensch, Amy B Heimberger, Melissa L Bondy
Immune cells of myeloid origin, including microglia, macrophages, and myeloid-derived suppressor cells adopt immunosuppressive phenotypes that support gliomagenesis. Here, we tested an a priori hypothesis that single nucleotide polymorphisms (SNPs) in genes related to glioma-associated myeloid cell regulation and function are also associated with patient survival after glioma diagnosis. Subjects for this study were 992 glioma patients treated at The University of Texas MD Anderson Cancer Center in Houston, Texas between 1992 and 2008...
September 30, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28875890/new-onset-diabetes-after-transplant-incidence-risk-factors-and-outcome
#3
S C Alagbe, A Voster, R Ramesar, C R Swanepoel
BACKGROUND: The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence...
August 25, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28868093/on-the-cellular-and-molecular-mechanisms-of-drug-induced-gingival-overgrowth
#4
Albert Ramírez-Rámiz, Lluís Brunet-LLobet, Eduard Lahor-Soler, Jaume Miranda-Rius
INTRODUCTION: Gingival overgrowth has been linked to multiple factors such as adverse drug effects, inflammation, neoplastic processes, and hereditary gingival fibromatosis. Drug-induced gingival overgrowth is a well-established adverse event. In early stages, this gingival enlargement is usually located in the area of the interdental papilla. Histologically, there is an increase in the different components of the extracellular matrix. OBJECTIVE: The aim of this manuscript is to describe and analyze the different cellular and molecular agents involved in the pathogenesis of Drug-induced gingival overgrowth...
2017: Open Dentistry Journal
https://www.readbyqxmd.com/read/28836585/population-pharmacokinetics-and-bayesian-estimation-of-mycophenolic-acid-concentrations-in-chinese-adult-renal-transplant-recipients
#5
Zi-Cheng Yu, Pei-Jun Zhou, Xiang-Hui Wang, Bressolle Françoise, Da Xu, Wei-Xia Zhang, Bing Chen
Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group)...
August 24, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28833329/population-pharmacokinetics-and-bayesian-estimation-of-tacrolimus-exposure-in-chinese-liver-transplant-patients
#6
B Chen, H-Q Shi, X-X Liu, W-X Zhang, J-Q Lu, B-M Xu, H Chen
WHAT IS KNOWN AND OBJECTIVES: Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling. METHODS: A total of 47 sets of rich-time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients...
August 17, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28814524/mutation-of-the-putative-immunosuppressive-domain-of-the-retroviral-envelope-glycoprotein-compromises-infectivity
#7
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 the 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...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#8
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
#9
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
#10
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, complete mucosal healing occurs in fewer 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 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28736028/association-between-tacrolimus-pharmacokinetics-and-cytochrome-p450-3a5-and-multidrug-resistance-protein-1-exon-21-polymorphisms
#11
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
#12
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
#13
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.
November 1, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28717926/clinical-evaluation-of-modified-release-and-immediate-release-tacrolimus-formulations
#14
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
#15
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
#16
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
#17
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
#18
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...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28646274/population-pharmacokinetic-modeling-of-diltiazem-in-chinese-renal-transplant-recipients
#19
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
#20
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
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