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Immunosuppression

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https://www.readbyqxmd.com/read/28346714/discrepant-serological-assays-for-pneumococcus-in-renal-transplant-recipients
#1
Jay A Fishman, David N Iklé, Robert A Wilkinson
Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype-specific capsular polysaccharides. Quantitative antibody levels (ELISA) and antibody-mediated opsonophagcytic assays (OPA) measure vaccine-induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein-conjugate vaccines (PCV) and polysaccharide vaccines (PSV)...
March 27, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28346662/intravenous-immunoglobulin-contributes-to-control-anti-melanoma-differentiation-associated-protein-5-mda5-antibody-associated-dermatomyositis-with-palmar-violaceous-macules-papules
#2
H Koguchi-Yoshioka, N Okiyama, K Iwamoto, Y Matsumura, T Ogawa, S Inoue, R Watanabe, M Fujimot
Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of dermatomyositis (DM) patients who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report 3 cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined modality therapy including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide, and immunoglobulins (IVIG)...
March 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#3
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#4
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346297/exposure-to-mycophenolate-and-fatherhood
#5
Karsten Midtvedt, Stein Bergan, Anna Varberg Reisæter, Bjørn Egil Vikse, Anders Åsberg
BACKGROUND: Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium and it is widely used after organ transplantation. In females taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by males exposed to MPA. METHODS: We compared outcomes in pregnancies fathered by renal transplant males per whether they had been exposed to MPA or not at time of conception...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28345769/best-practice-policy-statement-on-urodynamic-antibiotic-prophylaxis-in-the-non-index-patient
#6
REVIEW
Anne P Cameron, Lysanne Campeau, Benjamin M Brucker, J Quentin Clemens, Gregory T Bales, Michael E Albo, Michael J Kennelly
AIMS: Antibiotic prophylaxis before urodynamic testing (UDS) is widely utilized to prevent urinary tract infection (UTI) with only limited guidance. The Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) convened a Best Practice Policy Panel to formulate recommendations on the urodynamic antibiotic prophylaxis in the non-index patient. METHODS: Recommendations are based on a literature review and the Panel's expert opinion, with all recommendations graded using the Oxford grading system...
March 27, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28345768/mycophenolate-mofetil-and-rapamycin-induce-apoptosis-in-the-human-monocytic-u937-cell-line-through-two-different-pathways
#7
Maxime Nowak, Sylviane Tardivel, Thao Nguyen-Khoa, Sonia Abreu, Fatima Allaoui, Natalie Fournier, Pierre Chaminade, Jean-Louis Paul, Bernard Lacour
Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL...
March 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28345271/immunosuppression-with-mtor-inhibitors-prevents-the-development-of-donor-specific-antibodies-after-liver-transplant
#8
Katharina Willuweit, Andreas Heinold, Jassin Rashidi-Alavijeh, Falko M Heinemann, Peter A Horn, Andreas Paul, Guido Gerken, Kerstin Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are an important cause of complications after solid-organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined. METHODS: The DSA status of 400 patients who underwent LT at the outpatient clinic of the University Hospital Essen, was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity (MFI)...
March 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28345001/effective-depletion-of-pre-existing-anti-aav-antibodies-requires-broad-immune-targeting
#9
Victoria M Velazquez, Aaron S Meadows, Ricardo J Pineda, Marybeth Camboni, Douglas M McCarty, Haiyan Fu
Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344907/grape-seed-proanthocyanidin-extract-protects-lymphocytes-against-histone-induced-apoptosis
#10
Ping Chang, Bing Mo, David M Cauvi, Ying Yu, Zhenhui Guo, Jian Zhou, Qiong Huang, Qitao Yan, Guiming Chen, Zhanguo Liu
Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties...
2017: PeerJ
https://www.readbyqxmd.com/read/28344891/tumor-infiltrating-cd39-%C3%AE-%C3%AE-tregs-are-novel-immunosuppressive-t-cells-in-human-colorectal-cancer
#11
Guoming Hu, Pin Wu, Pu Cheng, Zhigang Zhang, Zhen Wang, Xiuyan Yu, Xuan Shao, Dang Wu, Jun Ye, Tao Zhang, Xiaochen Wang, Fuming Qiu, Jun Yan, Jian Huang
Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39(+) γδTreg in human colorectal cancer (CRC). CD39(+) γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4(+) or CD8(+) Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344879/prostaglandin-e2-mediated-adenosinergic-effects-on-cd14-cells-self-amplifying-immunosuppression-in-cancer
#12
Saly Al-Taei, Josephine Salimu, Lisa K Spary, Aled Clayton, Jason F Lester, Zsuzsanna Tabi
CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE- or blood-derived CD14(+) cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344872/intravenously-usable-fully-serotype-3-oncolytic-adenovirus-coding-for-cd40l-as-an-enabler-of-dendritic-cell-therapy
#13
Sadia Zafar, Suvi Parviainen, Mikko Siurala, Otto Hemminki, Riikka Havunen, Siri Tähtinen, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Akseli Hemminki
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting cells in the body, is a promising approach in cancer immunotherapy. However, tumors induce immunosuppression in their microenvironment that suppresses and impairs the function of DCs. Therefore, human clinical trials with DC therapy have often been disappointing. To improve the therapeutic efficacy and to overcome the major obstacles of DC therapy, we generated a novel adenovirus, Ad3-hTERT-CMV-hCD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344866/cd13-hi-neutrophil-like-myeloid-derived-suppressor-cells-exert-immune-suppression-through-arginase-1-expression-in-pancreatic-ductal-adenocarcinoma
#14
Jing Zhang, Xiongfei Xu, Min Shi, Ying Chen, Danghui Yu, Chenyan Zhao, Yan Gu, Biao Yang, Shiwei Guo, Guiling Ding, Gang Jin, Chin-Lee Wu, Minghua Zhu
Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344860/il-32-induces-indoleamine-2-3-dioxygenase-cd1c-dendritic-cells-and-indoleamine-2-3-dioxygenase-cd163-macrophages-relevance-to-mycosis-fungoides-progression
#15
Hanako Ohmatsu, Daniel Humme, Juana Gonzalez, Nicholas Gulati, Markus Möbs, Wolfram Sterry, James G Krueger
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c(+) myeloid dendritic cells (mDC) and/or CD163(+) macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344669/belimumab-in-systemic-lupus-erythematosus-sle-evidence-to-date-and-clinical-usefulness
#16
REVIEW
Sara Guerreiro Castro, David A Isenberg
Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease with multiple presentations, whose management presents many challenges. Many disease modifying or immunosuppressive drugs have been used with limited success, especially in patients with more severe disease activity. Belimumab is the first drug to be approved specifically for the treatment of SLE in more than 50 years. By blocking the B-cell activating factor, it interferes in B-cell differentiation and survival. Here we consider the results of the clinical trials that led to its approval, as well as the post-hoc analyses, follow-up studies and the current trials...
March 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28344477/development-and-characterization-of-methoxy-poly-ethylene-oxide-block-poly-%C3%AE%C2%B5-caprolactone-peo-b-pcl-micelles-as-vehicles-for-the-solubilization-and-delivery-of-tacrolimus
#17
Raisuddin Ali, Abubakar Farah, Ziyad Binkhathlan
Tacrolimus is a potent immunosuppressant; however, it suffers from several problems such as poor water solubility (4-12 μg/mL), low and variable oral bioavailability in patients, and narrow therapeutic window that could not be solved by the currently available i.v. formulation (Prograf®). Moreover, Prograf® contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions. Therefore, the aim of the present study was to investigate the potential of PEO-b-PCL polymeric micelles as alternative vehicles for the solubilization and delivery of tacrolimus...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344157/surgical-procedures-in-liver-transplant-patients-a-monocentric-retrospective-cohort-study
#18
Daniele Sommacale, Ganesh Nagarajan, Martin Lhuaire, Federica Dondero, Patrick Pessaux, Tullio Piardi, Alain Sauvanet, Reza Kianmanesh, Jacques Belghiti
BACKGROUND: Pre-existing chronic liver diseases and the complexity of the transplant surgery procedures lead to a greater risk of further surgery in transplanted patients compared to the general population. The aim of this monocentric retrospective cohort study was to assess the epidemiology of surgical complications in liver transplanted patients who require further surgical procedures and to characterize their post-operative risk of complications to enhance their medical care. PATIENTS AND METHODS: From January 1997 to December 2011, 1211 patients underwent orthotropic liver transplantation in our center...
March 23, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28344121/brevibacillus-laterosporus-pathogenesis-and-local-immune-response-regulation-in-the-house-fly-midgut
#19
Maria Elena Mura, Luca Ruiu
The insect midgut represents the primary site of action of the entompathogenic bacterium Brevibacillus laterosporus. Whilst most studies on this microorganism focus on the identification and characterization of possible virulence factors and toxins, little is known about the insect immune defense mechanisms that are activated against this pathogen. In this study we have investigated the local immune response of different house fly stages to B. laterosporus at the transcriptional level, and we tested the hypothesis that an improvement in entomopathogenicity can be achieved by impairing host innate immunity...
March 23, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28343227/what-is-the-key-to-improving-renal-transplant-recipients-awareness-of-skin-cancer-risk
#20
Alessandro Borghi, Monica Corazza, Yuri Battaglia, Elisa Maietti, Sara Minghetti, Annarosa Virgili
BACKGROUND: Previous studies have shown poor compliance rates regarding sun protection among organ transplant recipients. OBJECTIVE: The main objective of the present study was to assess the awareness among renal transplant recipients (RTRs) of their risk of non-melanoma skin cancer (NMSC) development and their sunscreen use. The influence of several potentially relevant variables was also assessed in order to identify possible weak points on which to concentrate efforts in this respect...
March 25, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
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