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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/28441386/graft-derived-cell-free-dna-a-noninvasive-early-rejection-and-graft-damage-marker-in-liver-transplantation-a-prospective-observational-multicenter-cohort-study
#1
Ekkehard Schütz, Anna Fischer, Julia Beck, Markus Harden, Martina Koch, Tilo Wuensch, Martin Stockmann, Björn Nashan, Otto Kollmar, Johannes Matthaei, Philipp Kanzow, Philip D Walson, Jürgen Brockmöller, Michael Oellerich
BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28435308/association-of-the-ppp3ca-c-249g-a-variant-with-clinical-outcomes-of-tacrolimus-based-therapy-in-kidney-transplant-recipients
#2
Patricia C Salgado, Fabiana Dv Genvigir, Claudia R Felipe, Helio Tedesco-Silva, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario Dc Hirata
BACKGROUND: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients. PATIENTS AND METHODS: A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28395107/ebv-positive-b-cell-proliferations-of-varied-malignant-potential-2015-sh-eahp-workshop-report-part-1
#3
Yasodha Natkunam, John R Goodlad, Amy Chadburn, Daphne de Jong, Dita Gratzinger, John K C Chan, Jonathan Said, Elaine S Jaffe
Objectives: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review B-cell proliferations of varied malignant potential associated with immunodeficiency. Methods: The Workshop Panel reviewed all cases of B-cell hyperplasias, polymorphic B-lymphoproliferative disorders, Epstein-Barr virus (EBV)-positive mucocutaneous ulcer, and large B-cell proliferations associated with chronic inflammation and rendered consensus diagnoses...
February 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340819/influence-of-proton-pump-inhibitors-on-mycophenolic-acid-pharmacokinetics-in-patients-with-renal-transplantation-and-the-relationship-with-cytochrome-2c19-gene-polymorphism
#4
H S Ciftci, M S Karadeniz, T Tefik, Y Caliskan, H Yazıcı, E Demir, A Turkmen, I Nane, F S Oguz, F Aydin
BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28326889/aquaporin-4-autoimmunity-in-patients-with-systemic-lupus-erythematosus-a-predominantly-population-based-study
#5
Nasrin Asgari, Sven Jarius, Helle Laustrup, Hanne Pb Skejoe, Soeren T Lillevang, Brian G Weinshenker, Anne Voss
BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28295266/cutaneous-phaeohyphomycosis
#6
Mariana P Caviedes, Ana C Torre, Maite Lisa Eliceche, Denise C Valdivia Monteros, Victoria I Volonteri, Ricardo L Galimberti
BACKGROUND: Phaeohyphomycosis is an infrequent infection in human beings. However, in recent years, its prevalence has augmented in immunosuppressed patients (mostly in solid organ transplanted patients). Infection can be mucocutaneous or disseminated. In the former, the fungus inoculation occurs mainly through traumatism. Lesions may be polymorphic and asymptomatic, isolated or multiple, and are usually localized in exposed areas of the limbs and head. Treatment is not standardized. When possible, surgical resection of the lesion is combined with systemic antifungals...
April 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28270648/relationship-of-serum-klotho-level-with-ace-gene-polymorphism-in-stable-kidney-allograft-recipients
#7
Maryam Zaare Nahandi, Mohamad Reza Ardalan, Ali Banagozar Mohamadi, Amir Ghorbani Haghjo, Morteza Jabbarpor Bonyadi, Tahere Mohamadian
INTRODUCTION: The kidney is the main source of serum Klotho production. Immunosuppressive agents could affect the kidney in this regard. The effect of the ACE gene polymorphism on Klotho production is a less studied area. This study aimed to assess serum Klotho and ACE gene in a group of stable kidney transplant recipients. MATERIALS AND METHODS: In a cross-sectional study, 30 kidney transplant recipients with stable allograft function and 27 healthy young individuals were assessed for their serum Klotho levels...
March 2017: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/28257625/association-of-il-10-gene-polymorphisms-and-susceptibility-to-juvenile-idiopathic-arthritis-in-egyptian-children-and-adolescents-a-case-control-study
#8
Manar M Fathy, Hosam F Elsaadany, Yasser F Ali, Mohsen A A Farghaly, Mohammed E Hamed, Hany E Ibrahim, Maha A Noah, Mayy A N Allah, Shaimaa S A Elashkar, Nasser I Abdelsalam, Hind M Abdelrahman, Ahmed R Ahmed, Heba G Anany, Sanaa M Ismail, Boshra R Ibrahim, Nashwa M Al Azizi, Heba H Gawish, Ghada M Al-Akad, Rehab M Nabil, Dalia S Fahmy, Salah F Alsayed
BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents...
January 17, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28247238/clinical-pharmacokinetic-monitoring-of-leflunomide-in-renal-transplant-recipients-with-bk-virus-reactivation-a-review-of-the-literature
#9
REVIEW
Joan C Y Ng, Marianna Leung, Alissa J Wright, Mary H H Ensom
Leflunomide is an immunosuppressive drug with in vitro and initial observational evidence of antiviral activity against BK virus (BKV), a pathogen that causes opportunistic infection upon reactivation in renal transplant recipients. Leflunomide is considered an ancillary option to immunosuppression reduction in the management of BKV reactivation. Plasma or blood concentrations of teriflunomide, the active metabolite of leflunomide, are commonly monitored because of high leflunomide doses being used, known inter-individual variability in pharmacokinetics, and hepatotoxicity risk...
February 28, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28245187/influence-of-genetic-polymorphisms-of-cyp3a5-and-abcb1-on-sirolimus-pharmacokinetics-patient-and-graft-survival-and-other-clinical-outcomes-in-renal-transplant
#10
Consuelo Rodríguez-Jiménez, Mar García-Saiz, Lourdes Pérez-Tamajón, Eduardo Salido, Armando Torres
BACKGROUND: In transplant patients receiving de novo anticalcineurin-free sirolimus (SRL)-based immunosuppression, we determined the influence of cytochrome P450 3A5 (CYP3A5) and ATP-binding cassette, sub-family B (MDR/TAP), member (ABCB1) genotypes on SRL blood levels and medium-term relevant clinical outcomes, in order to improve effectiveness of immunosuppression strategies when anti-mammalian target of rapamycin (anti-mTOR) inhibitor is indicated for clinical reasons. METHODS: Forty-eight renal transplant recipients (suffered 48% diabetes mellitus, 91% hypertension, and 47% dyslipidemia) were genotyped for CYP3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28195062/the-influence-of-the-tumor-necrosis-factor-alpa-308g-a-polymorphism-on-the-efficacy-of-immunosuppressive-therapy-in-patients-after-kidney-transplantation
#11
M M Kotowski, A Bogacz, J Bartkowiak-Wieczorek, J Sienko, D Procyk, K Dziewanowski, M Ostrowski, B Czerny, E Grzeskowiak, B Machalinski
Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28164520/the-effect-of-abcb1-polymorphisms-on-serial-tacrolimus-concentrations-in-stable-austrian-long-term-kidney-transplant-recipients
#12
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela Födinger
BACKGROUND: The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). METHODS: The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28162010/genetic-risk-factors-for-serious-infections-in-inflammatory-bowel-diseases
#13
Saranya Sasidharan, Vijay Yajnik, Hamed Khalili, John Garber, Ramnik Xavier, Ashwin N Ananthakrishnan
INTRODUCTION: Immunosuppression, the cornerstone of management of Crohn's disease (CD) and ulcerative colitis (UC) (inflammatory bowel diseases; IBD) is associated with an increased risk of serious infections that is inadequately predicted by clinical risk factors. The role of genetics in determining susceptibility to infections is unknown. METHODS: From a prospective-consented patient registry, we identified IBD patients with serious infections requiring hospitalization...
February 5, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28157558/genetic-polymorphism-of-interleukin-10-a592c-among-oral-cancer-with-squamous-cell-carcinoma
#14
Prithvi Kumar Singh, Mohammad Kaleem Ahmad, Vijay Kumar, Rajni Gupta, Monica Kohli, Amita Jain, Abbas Ali Mahdi, Jaishri Bogra, Girish Chandra
OBJECTIVE: Interleukin-10 (IL-10) is a pleiotropic cytokine with either immunosuppressive or immunostimulative activities. It has been reported that in cancer, the promoter region polymorphism of IL-10 (-A592C) alters both the expression and serum levels of this cytokine. In the present study, we have addressed the question as to whether the single nucleotide polymorphisms (SNPs) at positions -592 A/C in the IL-10 gene promoter, could predispose an individual to oral squamous cell carcinoma (OSCC)...
May 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28143491/-hla-g-3-utr-gene-polymorphisms-and-rheumatic-heart-disease-a-familial-study-among-south-indian-population
#15
Maheshkumar Poomarimuthu, Sivakumar Elango, Sambath Soundrapandian, Jayalakshmi Mariakuttikan
BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune disease where cross reactive CD4(+) T cells are involved in the pathogenesis of valvular damage. Human Leukocyte Antigen-G (HLA-G), an immunosuppressive molecule playing a crucial role in the inhibition of T cell response is associated with the pathogenesis of various autoimmune and inflammatory diseases. Genetic polymorphisms within the 3'untranslated region (UTR) of HLA-G influences its expression and thus disease pathogenesis...
February 1, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28134923/transforming-growth-factor-%C3%AE-1-functional-polymorphisms-in-myeloablative-sibling-hematopoietic-stem-cell-transplantation
#16
M Berro, M V Palau Nagore, M M Rivas, P Longo, C Foncuberta, A Vitriú, G Remaggi, J Martínez Rolon, G Jaimovich, A Requejo, L Feldman, K Padros, M B Rodríguez, B E Shaw, I Larripa, C B Belli, G D Kusminsky
Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9...
January 30, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28117944/infection-in-organ-transplantation
#17
REVIEW
J A Fishman
The prevention, diagnosis, and management of infectious disease in transplantation are major contributors to improved outcomes in organ transplantation. The risk of serious infections in organ recipients is determined by interactions between the patient's epidemiological exposures and net state of immune suppression. In organ recipients, there is a significant incidence of drug toxicity and a propensity for drug interactions with immunosuppressive agents used to maintain graft function. Thus, every effort must be made to establish specific microbiologic diagnoses to optimize therapy...
April 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28116196/a-rare-presentation-of-isolated-cns-posttransplantation-lymphoproliferative-disorder
#18
Jaime Morris, Casey Smith, Andrew Streicher, Allison Magnuson, Susan Newman, Robert Bertoli
Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28088792/impact-of-nudt15-polymorphisms-on-thiopurines-induced-myelotoxicity-and-thiopurines-tolerance-dose
#19
Dandan Yin, Xuyang Xia, Junlong Zhang, Shouyue Zhang, Fei Liao, Ge Zhang, Yan Zhang, Qianqian Hou, Xue Yang, Hong Wang, Zhigui Ma, Heyao Wang, Yiping Zhu, Wei Zhang, Yuelan Wang, Bo Liu, Lanlan Wang, Heng Xu, Yang Shu
Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076390/il-37-confers-protection-against-mycobacterial-infection-involving-suppressing-inflammation-and-modulating-t-cell-activation
#20
Haipeng Liu, Ruijuan Zheng, Peng Wang, Hua Yang, Xin He, Qun Ji, Wenjuan Bai, Hao Chen, Jianxia Chen, Wenxia Peng, Siyu Liu, Zhonghua Liu, Baoxue Ge
Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls...
2017: PloS One
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