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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/29691732/impact-of-the-cyp3a5-1-allele-on-the-pharmacokinetics-of-tacrolimus-in-japanese-heart-transplant-patients
#1
Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Akira Oita, Atsushi Kawase, Mitsutaka Takada
BACKGROUND AND OBJECTIVE: Tacrolimus, a major immunosuppressant used after transplantation, is associated with large interindividual variation involving genetic polymorphisms in metabolic processes. A common variant of the cytochrome P450 (CYP) 3A5 gene, CYP3A5*3, affects blood concentrations of tacrolimus. However, tacrolimus pharmacokinetics at the early stage of transplantation have not been adequately studied in heart transplantation. We retrospectively examined the impact of the CYP3A5 genotype on tacrolimus pharmacokinetics at the early stage of heart transplantation...
April 24, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29689130/a-donor-and-recipient-candidate-gene-association-study-of-allograft-loss-in-renal-transplant-recipients-receiving-a-tacrolimus-based-regimen
#2
Jean-Baptiste Woillard, Philippe Gatault, Nicolas Picard, Hélène Arnion, Dany Anglicheau, Pierre Marquet
This work investigated, in two large cohorts of French renal transplants treated with tacrolimus, the influence of donor and recipient ABCB1, CYP3A4 and CYP3A5 genotypes on the risk of allograft loss. A discovery and a replication population of 330 and 369 adult renal transplant patients, each from a different transplantation centre and all receiving a tacrolimus-based immunosuppressive regimen, were retrospectively genotyped. The influence of genetic factors and other known risk factors on allograft loss was investigated using multivariate Cox proportional hazard analyses...
April 24, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29679103/slc30a8-polymorphism-and-bmi-complement-hla-a-24-as-risk-factors-for-poor-graft-function-in-islet-allograft-recipients
#3
Else M Balke, Simke Demeester, DaHae Lee, Pieter Gillard, Robert Hilbrands, Ursule Van de Velde, Bart J Van der Auwera, Zhidong Ling, Bart O Roep, Daniël G Pipeleers, Bart Keymeulen, Frans K Gorus
AIMS/HYPOTHESIS: HLA-A*24 carriership hampers achievement of insulin independence in islet allograft recipients. However, less than half of those who fail to achieve insulin independence carry the allele. We investigated whether genetic polymorphism at the recipients' zinc transporter 8-encoding SLC30A8 gene (rs13266634) could complement their HLA-A*24 status in predicting functional graft outcome. METHODS: We retrospectively analysed data of a hospital-based patient cohort followed for 18 months post transplantation...
April 20, 2018: Diabetologia
https://www.readbyqxmd.com/read/29659047/the-changing-face-of-adult-posttransplant-lymphoproliferative-disorder-changes-in-histology-between-1999-2013
#4
Donald E Tsai, Stephen Bagley, Ran Reshef, Abraham Shaked, Roy D Bloom, Vivek Ahya, Lee Goldberg, Albert Chung, Fotini Debonera, Stephen J Schuster, Scott F Huntington
Posttransplant lymphoproliferative disorder (PTLD) typically presents with either polymorphic or monomorphic histology. While both are the end result of immunosuppressive therapies, their origins are felt to be different with different prognoses and responsiveness to therapy, resulting in two different malignancies. We attempted to confirm reports suggesting that the relative frequency of these two histologies is shifting over time. We analyzed 3040 adult PTLD cases in the UNOS OPTN database from 1999 to 2013...
April 16, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29644232/individualizing-immunosuppression-in-lung-transplantation
#5
REVIEW
Jennifer K McDermott, Reda E Girgis
Immunosuppression management after lung transplantation continues to evolve, with an increasing number of agents available for use in various combinations allowing for more choice and individualization of immunosuppressive therapy. Therapeutic developments have led to improved outcomes including lower acute rejection rates and improved survival. However, a one size fits all approach for any immunosuppressive strategy may not be best suited to the individual patient and ultimately patient specific factors must be considered when designing the immunosuppressive regimen...
March 14, 2018: Global Cardiology Science & Practice
https://www.readbyqxmd.com/read/29623066/combined-analysis-of-interleukin-10-gene-polymorphisms-and-protein-expression-in-children-with-cerebral-palsy
#6
Lei Xia, Mingjie Chen, Dan Bi, Juan Song, Xiaoli Zhang, Yangong Wang, Dengna Zhu, Qing Shang, Falin Xu, Xiaoyang Wang, Qinghe Xing, Changlian Zhu
Background: Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention. Objective: The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29621122/survival-time-to-biopsy-proven-acute-rejection-and-tacrolimus-adverse-drug-reactions-in-pediatric-liver-transplantation
#7
Natalia Riva, Marcelo Dip, Esteban Halac, Paulo Cáceres Guido, Jean Baptiste Woillard, Nieves Licciardone, Debora Chan, Jefferson Buendía, Daniela Borgnia, Andrea Bosaleh, María Teresa de Davila, Oscar Imventarza, Paula Schaiquevich
BACKGROUND: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin-American cohort of pediatric liver transplant patients...
April 3, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29609086/primary-central-nervous-system-hodgkin-lymphoma-like-post-transplant-lymphoproliferative-disorder
#8
Yusuke S Hori, Keina Nagakita, Yuki Ebisudani, Mizuho Aoi, Toru Fukuhara, Yoko Shinno
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a rare condition occurring after organ transplantation. PTLD comprises four subtypes, of which Hodgkin lymphoma (HL)-type and HL-like type (currently included in polymorphic type) account for only about 1%-3% of cases. Primary central nervous system PTLD is also rare, and most cases are Epstein-Barr virus-positive, B-cell PTLD, while no case of HL-like PTLD has yet been documented. CASE DESCRIPTION: We present a 43-year-old woman who underwent kidney transplantation for IgA nephropathy 14 years previously, and who presented to our Emergency Department with a chief complaint of seizure...
March 30, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29603629/cyp3a5-3-and-abcb1-61a-g-significantly-influence-dose-adjusted-trough-blood-tacrolimus-concentrations-in-the-first-three-months-post-kidney-transplantation
#9
Rong Hu, Daniel T Barratt, Janet K Coller, Benedetta C Sallustio, Andrew A Somogyi
Tacrolimus (TAC) is a first-line immunosuppressant used to prevent organ rejection after kidney transplantation. There is large inter-individual variability in its pharmacokinetics. Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolising enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2), and CYP3A co-factor cytochrome P450 reductase (POR), have been studied for their effects on tacrolimus disposition...
March 30, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29579330/impact-of-the-posttransplant-lymphoproliferative-disorder-subtype-on-survival
#10
Jean L Koff, Jing-Xia Li, Xinyan Zhang, Jeffrey M Switchenko, Christopher R Flowers, Edmund K Waller
BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set. METHODS: Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists...
March 26, 2018: Cancer
https://www.readbyqxmd.com/read/29563827/cyp3a5-polymorphisms-in-renal-transplant-recipients-influence-on-tacrolimus-treatment
#11
REVIEW
Lucy Chen, G V Ramesh Prasad
Tacrolimus is a commonly used immunosuppressant after kidney transplantation. It has a narrow therapeutic range and demonstrates wide interindividual variability in pharmacokinetics, leading to potential underimmunosuppression or toxicity. Genetic polymorphism in CYP3A5 enzyme expression contributes to differences in tacrolimus bioavailability between individuals. Individuals carrying one or more copies of the wild-type allele *1 express CYP3A5, which increases tacrolimus clearance. CYP3A5 expressers require 1...
2018: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29550576/influence-of-cyp3a5-genetic-differences-in-tacrolimus-on-quantitative-interstitial-fibrosis-and-long-term-graft-function-in-kidney-transplant-recipients
#12
Naoki Komine, Shigeru Satoh, Mitsuru Saito, Kazuyuki Numakura, Takamitsu Inoue, Hiroshi Tsuruta, Shintaro Narita, Atsushi Komatsuda, Hiroshi Nanjo, Hideaki Kagaya, Takenori Niioka, Masatomo Miura, Yoko Mitobe, Tomonori Habuchi
The impact of CYP3A5 polymorphisms on clinical outcomes is controversial. The present study investigated the impact of CYP3A5 genetic differences on the development of interstitial fibrosis (IF) from 0 h to 1 year post-transplantation in biopsy sections from 96 living kidney recipients under the same target trough regimen of tacrolimus. The relationships between CYP3A5 polymorphisms and long-term graft function and death-censored graft survival were also examined. A quantitative analysis of IF was performed using computer-assisted imaging on virtual slides...
March 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29532602/pantoprazole-induced-autoimmune-chronic-hepatitis
#13
Lucy Meunier, Jose Ursic-Bedoya, Georges-Philippe Pageaux, Dominique Larrey
BACKGROUND: Although very rare, pantoprazole can result in acute hepatitis. It has yet to be reported, however, that it can also cause chronic autoimmune hepatitis. AIM, METHOD AND RESULTS: We report the case of a patient in whom pantoprazole administration for 2 months was followed by acute liver injury with severe jaundice and features of autoimmunity. A liver biopsy revealed acute hepatocellular lesions associated with cholestasis, acute cholangitis and polymorphous inflammatory infiltration suggestive of drug-induced liver injury...
March 12, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29518251/low-5-year-cumulative-incidence-of-post-transplant-lymphoproliferative-disorders-after-solid-organ-transplantation-in-switzerland
#14
Raphael Steiner, Robert Kridel, Emiliano Giostra, Thomas McKee, Rita Achermann, Nicolas Mueller, Oriol Manuel, Michael Dickenmann, Macé M Schuurmans, Laurence de Leval, Thomas Fehr, Marianne Tinguely, Isabelle Binet, Sergio Cogliatti, Eugenia Haralamvieva, Michael Koller, The Swiss Transplant Cohort Study Stcs, Pierre-Yves Dietrich
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. METHODS: This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland...
March 8, 2018: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29484012/disseminated-porokeratosis-with-idiopathic-thrombocytopenia-case-report-and-literature-review-of-porokeratosis-and-related-disorders
#15
Anastasiya Atanasova Chokoeva, Uwe Wollina, Torello Lotti, Georgi Konstantinov Maximov, Ilia Lozev, Georgi Tchernev
BACKGROUND: Porokeratosis is characterised by one or more atrophic patches surrounded by a distinctive peripheral keratotic ridge, typically found on sun-exposed areas, with several clinical variants and typical histological findings. Despite ultraviolet radiation, varies antibody - related autoimmune disease treated with systemic steroids and other immunosuppressive conditions such as chronic liver disease, HIV and organ transplantations have been implicated in its etiopathology. CASE REPORT: We present a case of porokeratosis, associated with idiopathic thrombocytopenia in 74 - year old, otherwise healthy male patient, as we discuss the previously reported associated disorders...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29470609/-new-aspects-in-systemic-treatment-of-atopic-dermatitis
#16
REVIEW
T Werfel, A Wollenberg, T Pumnea, A Heratizadeh
In severe cases of atopic dermatitis (AD) systemic treatment is indicated. So far, cyclosporine and systemic glucocorticosteroids represented the only systemic treatment options approved for the indications of AD in Germany; however, from clinical practice there is increasing evidence for beneficial therapeutic effects in AD by other immunosuppressive or immunomodulatory substances, such as mycophenolate, methotrexate, alitretinoin and ustekinumab. Beyond this, ongoing research activities focus on a better understanding of genetic and immunological aspects of this chronic inflammatory skin disease...
February 22, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29454824/candida-albicans-biology-molecular-characterization-pathogenicity-and-advances-in-diagnosis-and-control-an-update
#17
REVIEW
Maryam Dadar, Ruchi Tiwari, Kumaragurubaran Karthik, Sandip Chakraborty, Youcef Shahali, Kuldeep Dhama
Candida albicans is an emerging multidrug-resistant fungal pathogen representing an important source of invasive disease in humans and generating high healthcare costs worldwide. This fungus is frequently found in different anatomical sites of healthy persons and could induce systemic and superficial infections under optimal environmental conditions. Invasive candidiasis (IC) is an important nosocomial infection with high morbidity and mortality rates in hospitalized children. It represents a major source of prolonged infections in intensive care unit (ICU), particularly in immunosuppressed or elderly patients...
April 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29454235/donor-and-recipient-p450-gene-polymorphisms-influence-individual-pharmacological-effects-of-tacrolimus-in-chinese-liver-transplantation-patients
#18
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
April 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29438108/stat3-enhancing-germline-mutations-contribute-to-tumor-extrinsic-immune-evasion
#19
Daniel Kogan, Alexander Grabner, Christopher Yanucil, Christian Faul, Vijay Kumar Ulaganathan
Immune evasion and the suppression of antitumor responses during cancer progression are considered hallmarks of cancer and are typically attributed to tumor-derived factors. Although the molecular basis for the crosstalk between tumor and immune cells is an area of active investigation, whether host-specific germline variants can dictate immunosuppressive mechanisms has remained a challenge to address. A commonly occurring germline mutation (c.1162G>A/rs351855 G/A) in the FGFR4 (CD334) gene enhances signal transducer and activator of transcription 3 (STAT3) signaling and is associated with poor prognosis and accelerated progression of multiple cancer types...
April 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29423114/germline-polymorphism-of-interferon-lambda3-is-clinically-associated-with-progression-of-renal-cell-carcinoma
#20
Akinori Nukui, Yoshiaki Yanai, Toyonori Tsuzuki, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
Renal cell carcinoma (RCC) is an immunogenic tumor that shows a metabolic shift to aerobic glycolysis. The immune system can have opposing host-protective and tumor-promoting effects, and aerobic glycolysis suppresses antitumor immunity. In addition to immunostimulatory effect, increasing numbers of studies have revealed that interferon (IFN) is also involved in promoting immunosuppression. Since various single nucleotide polymorphisms (SNPs) can influence the outcome of anticancer therapy, we investigated SNPs for IFN-lambda3, a new member of IFN family, in 53 patients with metastatic RCC who underwent cytoreductive nephrectomy...
January 9, 2018: Oncotarget
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