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Polymorphism and immunosuppression

Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Zheng Jiao, Ming Zhang, Mingkang Zhong
PURPOSE: The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. METHODS: Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis...
October 17, 2016: European Journal of Clinical Pharmacology
Marta Wieczorek, Annette Czernik
Paraneoplastic pemphigus (PNP) is a fatal autoimmune blistering disease associated with an underlying malignancy. It is a newly recognized blistering disease, which was first recognized in 1990 by Dr Anhalt who described an atypical pemphigus with associated neoplasia. In 2001, Nguyen proposed the term paraneoplastic autoimmune multiorgan syndrome because of the recognition that the condition affects multiple organ systems. PNP presents most frequently between 45 and 70 years old, but it also occurs in children and adolescents...
2016: Clinical, Cosmetic and Investigational Dermatology
Marica Grskovic, David J Hiller, Lane A Eubank, John J Sninsky, Cindy Christopherson, John P Collins, Kathryn Thompson, Mindy Song, Yue S Wang, David Ross, Mitchell J Nelles, James P Yee, Judith C Wilber, Maria G Crespo-Leiro, Susan L Scott, Robert N Woodward
The use of circulating cell-free DNA (cfDNA) as a biomarker in transplant recipients offers advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection and immunosuppression optimization. However, the fraction of donor-derived cfDNA (dd-cfDNA) in transplant recipient plasma is low and challenging to quantify. Previously reported methods to measure dd-cfDNA require donor and recipient genotyping, which is impractical in clinical settings and adds cost. We developed a targeted next-generation sequencing assay that uses 266 single-nucleotide polymorphisms to accurately quantify dd-cfDNA in transplant recipients without separate genotyping...
October 7, 2016: Journal of Molecular Diagnostics: JMD
M Khosravi, I Saadat, M H Karimi, S A Malek Hosseini
BACKGROUND: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs...
2016: International Journal of Organ Transplantation Medicine
Ayumi Asada, Shigeki Bamba, Yukihiro Morita, Kenichiro Takahashi, Hirotsugu Imaeda, Atsushi Nishida, Osamu Inatomi, Mitsushige Sugimoto, Masaya Sasaki, Akira Andoh
BACKGROUND: Tacrolimus is an immunosuppressive agent, used in the remission induction therapy of ulcerative colitis (UC). AIMS: We investigated the correlation between CYP3A5 genetic polymorphisms and the adverse events in patients with UC. The pharmacokinetics of tacrolimus after oral administration were also analyzed. METHODS: We enrolled 29 hospitalized patients with UC received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed using Custom TaqMan(®) SNP genotyping assays...
September 21, 2016: Digestive and Liver Disease
Evangelos J Giamarellos-Bourboulis, Steven M Opal
During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells...
September 2016: Annals of Translational Medicine
Ji Won In, Nuri Lee, Eun Youn Roh, Sue Shin, Kyoung Un Park, Eun Young Song
OBJECTIVES: Aplastic anemia (AA) is characterized by pancytopenia and bone marrow failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells (Tregs) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is a major regulator for the development and function of Tregs. Polymorphism in FoxP3 was shown to be associated with various autoimmune diseases, however, has not yet been studied in AA. In this study, we examined the association between FoxP3 polymorphisms and AA in Korean patients...
October 5, 2016: Hematology (Amsterdam, Netherlands)
Anthea Brennan, Shannon L Donahoe, Julia A Beatty, Katherine Belov, Scott Lindsay, Katherine A Briscoe, Jan Šlapeta, Vanessa R Barrs
Whether Toxoplasma gondii genotype is associated with disease severity in naturally occurring toxoplasmosis in domestic cats is unknown. The aim of this study was to compare genotypes of T. gondii in latently infected cats with those in cats with clinical toxoplasmosis. Results of a PCR targeting the B1 gene to detect T. gondii DNA were positive in tissue samples from 11 of 17 (65%) seropositive cats tested including four with clinical toxoplasmosis and seven with latent infections, as determined by serology, histologic findings and immunohistochemistry...
September 15, 2016: Veterinary Parasitology
Asha Rani, Ravi Ranjan, Halvor S McGee, Ahmed Metwally, Zahraa Hajjiri, Daniel C Brennan, Patricia W Finn, David L Perkins
Recent studies have established that the human urine contains a complex microbiome, including a virome about which little is known. Following immunosuppression in kidney transplant patients, BK polyomavirus (BKV) has been shown to induce nephropathy (BKVN), decreasing graft survival. In this study we investigated the urine virome profile of BKV+ and BKV- kidney transplant recipients. Virus-like particles were stained to confirm the presence of VLP in the urine samples. Metagenomic DNA was purified, and the virome profile was analyzed using metagenomic shotgun sequencing...
2016: Scientific Reports
Agnieszka Wójtowicz, Pierre-Yves Bochud
Patients undergoing haematopoietic stem cell transplantation (HSCT) are highly exposed to infectious agents. However, it is not known why certain HSCT recipients rapidly develop severe infections while other, despite similar immunosuppressive conditions, do not. Increasing evidence suggests that such differences may be due, in part, to polymorphisms in immune genes. Thus, the identification of genetic factors influencing susceptibility to infections in HSCT recipients may lead to the development of individualized management strategies...
September 9, 2016: Virulence
Shan Liu, Qing Li, Ying Zhang, Qiushuang Li, Baodong Ye, Dijiong Wu, Li Wu, Hanti Lu, Conghua Ji
This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched...
2016: PloS One
J Ge, J Wang, H Zhao, K Li, Y Jing, G Li
INTRODUCTION: Tacrolimus is an immunosuppressive medication for organ transplantation. FOXP3(+) T regulatory cells (Tregs) play roles in suppression of rejection and induction of graft tolerance. This study aimed to evaluate the correlation between the polymorphism of FOXP3 and the blood level of tacrolimus in renal transplant recipients. METHODS: This retrospective study included 100 renal transplant recipients receiving tacrolimus treatment and 100 healthy control subjects...
July 2016: Transplantation Proceedings
Nazan Atalan, Hande Karagedik, Leyla Acar, Selim Isbir, Seda Gulec Yilmaz, Arzu Ergen, Turgay Isbir
AIM: To analyze the effect of TLR-9 (-1486 T>C) and TLR-9 (C>T) gene polymorphisms both at TLR-9 levels and together with their sepsis parameters. In this regard, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used in order to detect TLR-9 gene polymorphisms, whereas the ELISA technique was used to analyze TLR-9 serum levels in 80 sepsis patients and 100 healthy individuals. MATERIALS AND METHODS: The study group consisted of 80 patients with a diagnosis of sepsis and 100 healthy individuals...
September 2016: In Vivo
VijayKumar Patra, Scott N Byrne, Peter Wolf
Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response...
2016: Frontiers in Microbiology
Stacey A Maskarinec, Melissa D Johnson, John R Perfect
The development of severe fungal infections has long been associated with traditional risk factors such as profound immunosuppression, yet it remains challenging to understand why under similar conditions only some patients will develop these infections while others will not. Recent studies have demonstrated the importance of host genetic variation in influencing the severity and susceptibility to invasive fungal infections (IFIs). In this review, we examine selected primary immunodeficiencies characterized by their vulnerability to a narrow range of fungal pathogens, and then focus on recently identified genetic polymorphisms associated with an increased susceptibility to IFIs...
June 2016: Current Clinical Microbiology Reports
Vladimir Tesar, Zdenka Hruskova
BACKGROUND: Lupus nephritis (LN) is still associated with significant mortality and substantial risk of progression to end-stage renal failure. Its outcome is related to the class and severity of LN and response to treatment, and it is poorer in patients with renal relapses. Ethnicity has a relatively well-defined impact on the outcome of the patients and their response to treatment and must always be taken into consideration in treatment decisions. SUMMARY: In this article, we provide a review of the impact of ethnicity on the prevalence of systemic lupus erythematosus (SLE), the proportion of patients with SLE developing LN, outcomes of SLE and LN and response of LN to treatment...
September 2015: Kidney Diseases
Desmond Y H Yap, Tak Mao Chan
BACKGROUND: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. SUMMARY: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed...
September 2015: Kidney Diseases
Maria Isabel Carvalho, Isabel Pires, Justina Prada, Hugo Gregório, Luis Lobo, Felisbina L Queiroga
The activity of regulatory T cells (Tregs) is closely associated with the expression of FoxP3 transcription factor. FoxP3 regulatory T cells (FoxP3Treg) have immunosuppressive properties and can work for prevention of harmful autoimmune responses, however can also interfere with beneficial anti-tumor immunity. In human breast cancer these cells play a crucial role in tumor progression. In canine mammary tumors (CMT) this topic is not well-documented. This study included 80 malignant CMT and studied, by immunohistochemistry, the intratumoral FoxP3 expression together with microvessel density (MVD), vascular endothelial growth factor (VEGF) and several clinicopathological characteristics...
October 1, 2016: Veterinary Immunology and Immunopathology
Laure Gineau, David Courtin, Mamadou Camara, Hamidou Ilboudo, Vincent Jamonneau, Fabricio C Dias, Leonidas Tokplonou, Jacqueline Milet, Priscila B Mendonça, Erick C Castelli, Oumou Camara, Mariam Camara, Benoit Favier, Nathalie Rouas-Freiss, Philippe Moreau, Eduardo A Donadi, Bruno Bucheton, Audrey Sabbagh, André Garcia
BACKGROUND:  Human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense can be diagnosed in the early hemolymphatic stage (stage 1 [S1]) or meningoencephalitic stage (stage 2 [S2]). Importantly, individuals harbouring high and specific antibody responses to Tbg antigens but negative parasitology are also diagnosed in the field (seropositive [SERO]). Whereas some develop the disease in the months following their initial diagnosis (SERO/HAT), others remain parasitologically negative for long periods (SERO) and are apparently able to control infection...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Shirin Farahyar, Farideh Zaini, Parivash Kordbacheh, Sassan Rezaie, Mehraban Falahati, Mahin Safara, Reza Raoofian, Kamran Hatami, Masoumeh Mohebbi, Mansour Heidari
Acquired azole resistance in opportunistic fungi causes severe clinical problems in immunosuppressed individuals. This study investigated the molecular mechanisms of azole resistance in clinical isolates of Candida glabrata. Six unmatched strains were obtained from an epidemiological survey of candidiasis in immunocompromised hosts that included azole and amphotericin B susceptible and azole resistant clinical isolates. Candida glabrata CBS 138 was used as reference strain. Antifungal susceptibility testing of clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) methods...
July 2016: Acta Medica Iranica
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