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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/29885912/buccal-paraneoplastic-pemphigus-multi-resistant-case-report-and-review-of-diagnostic-and-therapeutic-strategies
#1
J Decaux, I Ferreira, P Van Eeckhout, C Dachelet, M Magremanne
Paraneoplastic pemphigus is a rare autoimmune blistering disease generally associated with malignancy. The clinical presentation consists typically of painful and diffuse erosive stomatitis that may be accompanied by polymorphic skin lesions and systemic involvement. Diagnosis is based on clinical manifestations and confirmed by histology and immunological testing. The current first-line treatment is systemic corticosteroids and adjuvant therapies, including immunosuppressive agents. We report a case of buccal paraneoplastic pemphigus resistant to ibrutinib and rituximab successfully treated with azathioprine and polyclonal immunoglobulins...
June 7, 2018: Journal of Stomatology, Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29867953/association-between-promoter-polymorphisms-in-cd46-and-cd59-in-kidney-donors-and-transplant-outcome
#2
Laura A Michielsen, Arjan D van Zuilen, Tineke Kardol-Hoefnagel, Marianne C Verhaar, Henny G Otten
Complement regulating proteins, including CD46, CD55, and CD59, protect cells against self-damage. Because of their expression on the donor endothelium, they are hypothesized to be involved in accommodation. Polymorphisms in their promoter regions may affect their expression. The aim of this study was to investigate if donor polymorphisms in complement regulating proteins influence kidney transplant outcomes. We included 306 kidney transplantations between 2005 and 2010. Five polymorphisms in the promoters of CD46, CD55, and CD59 were genotyped...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29809322/fetal-hla-g-alleles-and-their-effect-on-miscarriage
#3
Altug Koc, Ozgur Kirbiyik, Yasar B Kutbay, Berk Ozyilmaz, Taha R Ozdemir, Ozge Ozer Kaya, Gozde Kubat, Zeynep Peker Koc
BACKGROUND: Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels...
May 29, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29801578/the-pharmacogenetics-of-immune-modulating-therapy
#4
Ingolf Cascorbi
Immunosuppressive drugs are a prerequisite in organ transplantation to prevent rejection and are also widely used in inflammatory diseases such as inflammatory bowel disease (IBD) or also in some hematologic malignancies-depending on the mode of action. For thiopurine analogs the polymorphic thiopurine S-methyltransferase (TPMT) was early detected to be associated with thiopurine-induced leukopenia; recent studies identified also NUDT15 to be related to this severe side effect. For drugs like methotrexate and mycophenolate mofetil a number of ADME genes like UDP-glucuronosyltransferases (UGTs) and ABC efflux transporters were investigated, however, with partly contradicting results...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29797086/management-of-non-diffuse-large-b-cell-lymphoma-post-transplant-lymphoproliferative-disorder
#5
REVIEW
Ajay Major, Manali Kamdar
Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion...
May 24, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29765143/other-immunomodulatory-agent-related-lymphoproliferative-diseases-a-single-center-series-of-72-biopsy-confirmed-cases
#6
Lukas Marcelis, Charlien Berghen, Alexandra De Zutter, Pauline Biesemans, Peter Vandenberghe, Gregor Verhoef, Olivier Gheysens, Xavier Sagaert, Daan Dierickx, Thomas Tousseyn
Ongoing development of new drugs, as well as novel indications in the treatment of autoimmune diseases leads to the increasing use of immunomodulatory and immunosuppressive drugs. Immunomodulatory agent-related lymphoproliferative disorders are a known and potentially life threatening complication of chronic administration of these drugs, but are less well characterized compared with post-transplant lymphoproliferative disorders. The heterogeneous drug targets, various underlying disease indications, different drug combinations used and relatively low incidence render data collection and interpretation difficult...
May 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29754746/rs3212227-snp-in-the-il12b-gene-prevents-delayed-graft-function-after-kidney-transplantation
#7
Vladimir Perovic, Milos Markovic, Milica Kravljaca, Emina Milosevic, Milica Djoric, Vera Pravica, Radomir Naumovic
BACKGROUND AND AIMS: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients...
May 10, 2018: Archives of Medical Research
https://www.readbyqxmd.com/read/29754218/genetic-variants-in-the-hla-class-ii-region-associated-with-risk-of-cutaneous-squamous-cell-carcinoma
#8
Wei Wang, Hanna M Ollila, Alice S Whittemore, Shadmehr Demehri, Nilah M Ioannidis, Eric Jorgenson, Emmanuel Mignot, Maryam M Asgari
BACKGROUND: The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated...
May 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29731062/cyp3a5-3-genetic-polymorphism-and-tacrolimus-concentration-in-myanmar-renal-transplant-patients
#9
Y Y Htun, H K Swe, T M Saw
BACKGROUND: Genetic polymorphism is an important factor that influences tacrolimus concentrations and has the potential to predict the optimal dosage of tacrolimus in personalized medicine. Tacrolimus, a drug of narrow therapeutic index, is used in renal transplant recipients as an immunosuppressant agent. It is a substrate of cytochrome P450 3A (CYP3A) and has highly variable pharmacokinetic parameters. OBJECTIVE: The aim of this study was to identify the proportion of CYP3A5 gene polymorphism in Myanmar kidney transplant recipients and to determine the impact of CYP3A5 gene polymorphisms on tacrolimus level in CYP3A5 expressors and nonexpressors...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29720911/association-between-thiopurine-s-methyltransferase-tpmt-genetic-variants-and-infection-in-pediatric-heart-transplant-recipients-treated-with-azathioprine-a-multi-institutional-analysis
#10
Dionna J Green, Son Q Duong, Gilbert J Burckart, Tristan Sissung, Douglas K Price, William D Figg, Maria M Brooks, Richard Chinnock, Charles Canter, Linda Addonizio, Daniel Bernstein, David C Naftel, Adriana Zeevi, James K Kirklin, Steven A Webber, Brian Feingold
OBJECTIVES: Bone marrow suppression is a common adverse effect of the immunosuppressive drug azathioprine. Polymorphisms in the gene encoding thiopurine S -methyltransferase (TPMT) can alter the metabolism of azathioprine, resulting in marrow toxicity and life-threatening infection. In a multicenter cohort of pediatric heart transplant (HT) recipients, we determined the frequency of TPMT genetic variation and assessed whether azathioprine-treated recipients with TPMT variants were at increased risk of infection...
March 2018: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29708622/evaluation-of-tacrolimus-related-cyp3a5-genotyping-in-china-results-from-the-first-external-quality-assessment-exercise
#11
Guigao Lin, Xiao Zhang, Kuo Zhang, Yanxi Han, Liming Tan, Jinming Li
BACKGROUND: Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus. METHODS: To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping...
April 30, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29704867/azathioprine-induced-alopecia-and-leukopenia-associated-with-nudt15-polymorphisms
#12
H Nomura, Y Kurihara, M Saito, A Fukushima, Y Shintani, R Shiiyama, S Toshima, A Kamata, J Yamagami, T Funakoshi, K Kameyama, M Amagai, A Kubo, N Umegaki-Arao
Azathioprine (AZA), a widely used immunosuppressant, can induce cytotoxic effects including myelosuppression and alopecia.1 Recent studies revealed that polymorphisms of NUDT15 are associated with thiopurine-induced alopecia and leukopenia.2-5 The frequency of NUDT15 polymorphisms in East and South Asians is high (22.6% and 13.6%, respectively).5 Thus, adverse event management during AZA treatment is essential for Asian populations with these polymorphisms. This article is protected by copyright. All rights reserved...
April 28, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29702976/nudt15-r139c-variation-increases-the-risk-of-azathioprine-induced-toxicity-in-chinese-subjects-case-report-and-literature-review
#13
Xiang Fei, Qing Shu, Bing-Zhu Hua, Shi-Ying Wang, Zhi-Yong Chen, Wei-Hong Ge, Yun Fang
INTRODUCTION: Azathioprine (AZA) is widely used as an immunosuppressive agent, and its efficacy has been recommended by many clinical studies. However, leukopenia, the most common toxicity, still restricts its clinical applications. Recent studies found that NUDT15 R139C polymorphism is strongly associated with AZA-induced leukopenia in Koreans. However, the follow-up studies available are all limited to inflammatory bowel disease (IBD). Here, we report a case of a Chinese patient with Sjögren syndrome (SS) with wild-type TPMT*3C who was diagnosed with AZA-induced severe toxicity due to NUDT15 mutation based on clinical and laboratory characteristics...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29691732/impact-of-the-cyp3a5-1-allele-on-the-pharmacokinetics-of-tacrolimus-in-japanese-heart-transplant-patients
#14
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
#15
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 center 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
#16
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...
July 2018: Diabetologia
https://www.readbyqxmd.com/read/29659047/the-changing-face-of-adult-posttransplant-lymphoproliferative-disorder-changes-in-histology-between-1999-and-2013
#17
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 2 different malignancies. We attempted to confirm reports suggesting that the relative frequency of these 2 histologies is shifting over time. We analyzed 3040 adult PTLD cases in the UNOS OPTN database from 1999 to 2013. Changes in PTLD cases over time were analyzed for histology, time from transplant to diagnosis, and patient EBV serostatus...
April 16, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29644232/individualizing-immunosuppression-in-lung-transplantation
#18
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
#19
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
#20
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
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