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https://www.readbyqxmd.com/read/28637300/commercial-rodent-diets-differentially-regulate-autoimmune-glomerulonephritis-epigenetics-and-microbiota-in-mrl-lpr-mice
#1
Michael R Edwards, Rujuan Dai, Bettina Heid, Thomas E Cecere, Deena Khan, Qinghui Mu, Catharine Cowan, Xin M Luo, S Ansar Ahmed
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone rich soy and alfalfa, Harlan 2018 isoflavone rich soy-based diet, or ResearchDiets Inc...
June 15, 2017: International Immunology
https://www.readbyqxmd.com/read/28635253/discovery-and-characterization-of-histidine-oxidation-initiated-cross-links-in-an-igg1-monoclonal-antibody
#2
Chong-Feng Xu, Rachel Chen, Linda Yi, Tim Brantley, Brad Stanley, Zoran Sosic, Li Zang
Novel cross-links between an oxidized histidine and intact histidine, lysine or cysteine were discovered and characterized from high-molecular weight (HMW) fractions of an IgG1 monoclonal antibody (mAb). The mAb HMW fractions were col-lected using preparative size-exclusion chromatography (SEC) and extensively characterized to understand the mechanism of formation of the non-reducible and covalently linked portion of the HMWs. The HMW fractions were IdeS digested, reduced and analyzed by size-exclusion chromatography coupled with mass spectrometry (SEC-MS)...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28634748/exposure-response-relationship-of-ramucirumab-in-east-asian-patients-from-rainbow-a-randomized-clinical-trial-in-second-line-treatment-of-gastric-cancer
#3
Tae You Kim, Chia-Jui Yen, Salah-Eddin Al-Batran, David Ferry, Ling Gao, Yanzhi Hsu, Rebecca Cheng, Mauro Orlando, Atsushi Ohtsu
BACKGROUND: Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m(2) paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure-response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial...
June 20, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28634654/improvement-in-latent-variable-indirect-response-modeling-of-multiple-categorical-clinical-endpoints-application-to-modeling-of-guselkumab-treatment-effects-in-psoriatic-patients
#4
Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou
Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23...
June 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28634480/fc-galactosylation-of-human-immunoglobulin-gamma-isotypes-improves-c1q-binding-and-enhances-complement-dependent-cytotoxicity
#5
Benjamin Peschke, Christian W Keller, Patrick Weber, Isaak Quast, Jan D Lünemann
Binding of the complement component C1q to the CH2 domain of antigen-bound immunoglobulin gamma (IgG) activates the classical complement pathway and depends on its close proximity to Fc fragments of neighboring antibodies. IgG subclasses contain a highly conserved asparagine 297 (N)-linked biantennary glycan within their CH2 domains, the core structure of which can be extended with terminal galactose and sialic acid residues. To investigate whether Fc-glycosylation regulates effector functions of human IgG subclasses, we cloned the antigen-binding region of the CD20-specific monoclonal antibody rituximab into IgG isotype expression vectors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28632956/anti-inflammatory-potential-of-a-heat-killed-lactobacillus-strain-isolated-from-kimchi-on-house-dust-mite-induced-atopic-dermatitis-in-nc-nga-mice
#6
C Y Choi, Y H Kim, S Oh, H J Lee, J H Kim, S H Park, H J Kim, S J Lee, T Chun
AIMS: Atopic dermatitis (AD) is an allergic skin disease driven by the Th2-prone immune response. Therefore, a fundamental approach to restoring the Th1/Th2 balance is needed to treat AD. METHODS AND RESULTS: Eighteen different Lactobacillus strains isolated from Kimchi were screened to identify those that stimulated immune cells to secret Th1-type or Th2-type cytokines. Lactobacillus brevis NS1401 induced the greatest IFN-γ and IL-12 secretion and the least IL-4 production among the tested Lactobacillus strains...
June 20, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28629726/th2-related-immune-responses-by-the-brucella-abortus-cellular-antigens-malate-dehydrogenase-elongation-factor-and-arginase
#7
Young Bin Im, Soojin Shim, Woo Bin Park, Suk Kim, Han Sang Yoo
Brucellosis is an important zoonotic disease caused by Brucella species. The disease is difficult to control due to the intracellular survival of the bacterium and the lack of precise understanding of pathogenesis. Despite of continuous researches on the pathogenesis of Brucella spp. infection, there is still question on the pathogenesis, especially earlier immune response in the bacterial infection. Malate dehydrogenase (MDH), elongation factor (Tsf), and arginase (RocF), which showed serological reactivity, were purified after gene cloning, and their immune modulating activities were then analyzed in a murine model...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28628042/a-therapeutic-t-cell-receptor-mimic-antibody-targets-tumor-associated-prame-peptide-hla-i-antigens
#8
Aaron Y Chang, Tao Dao, Ron S Gejman, Casey A Jarvis, Andrew Scott, Leonid Dubrovsky, Melissa D Mathias, Tatyana Korontsvit, Victoriya Zakhaleva, Michael Curcio, Ronald C Hendrickson, Cheng Liu, David A Scheinberg
Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that is expressed in many cancers and leukemias. In healthy tissue, PRAME expression is limited to the testes and ovaries, making it a highly attractive cancer target. PRAME is an intracellular protein that cannot currently be drugged. After proteasomal processing, the PRAME300-309 peptide ALYVDSLFFL (ALY) is presented in the context of human leukocyte antigen HLA-A*02:01 molecules for recognition by the T cell receptor (TCR) of cytotoxic T cells...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28626461/neoglycoconjugate-of-tetrasaccharide-representing-one-repeating-unit-of-the-streptococcus-pneumoniae-type-14-capsular-polysaccharide-induces-the-production-of-opsonizing-igg1-antibodies-and-possesses-the-highest-protective-activity-as-compared-to-hexa-and-octasaccharide
#9
Ekaterina A Kurbatova, Nelli K Akhmatova, Elina A Akhmatova, Nadezhda B Egorova, Natalya E Yastrebova, Elena V Sukhova, Dmitriy V Yashunsky, Yury E Tsvetkov, Marina L Gening, Nikolay E Nifantiev
Identifying protective synthetic oligosaccharide (OS) epitopes of Streptococcus pneumoniae capsular polysaccharides (CPs) is an indispensable step in the development of third-generation carbohydrate pneumococcal vaccines. Synthetic tetra-, hexa-, and octasaccharide structurally related to CP of S. pneumoniae type 14 were coupled to bovine serum albumin (BSA), adjuvanted with aluminum hydroxide, and tested for their immunogenicity in mice upon intraperitoneal prime-boost immunizations. Injections of the conjugates induced production of opsonizing anti-OS IgG1 antibodies (Abs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28625522/immunogenicity-and-therapeutic-effects-of-recombinant-ag85ab-fusion-protein-vaccines-in-mice-infected-with-mycobacterium-tuberculosis
#10
Yan Liang, Junxian Zhang, Yourong Yang, Xuejuan Bai, Qi Yu, Ning Li, Ying Hou, Yingchang Shi, Lan Wang, Xueqiong Wu
The immune function of tuberculosis (TB) patients is disordered. By using immune regulators to assist chemotherapy for TB the curative effect might be improved. In this study, a vaccine containing Mycobacterium tuberculosis (M. tuberculosis) recombinant Ag85AB fusion protein (rAg85AB) was constructed and evaluated. The mice were immunized intramuscularly three times at two-week intervals with Ag85AB fusion protein combined with Corynebacterium parvum adjuvant (rAg85AB+CP). In comparison to control mice that received either CP alone or saline, the mice that received rAg85AB+CP had significantly higher number of T cells secreting IFN-γ and higher levels of specific antibodies of IgG, IgG1 and IgG2a isotypes in sera...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28623267/a-new-paradigm-for-antiangiogenic-therapy-through-controlled-release-of-bevacizumab-from-plga-nanoparticles
#11
Flávia Sousa, Andrea Cruz, Pedro Fonte, Inês Mendes Pinto, Maria Teresa Neves-Petersen, Bruno Sarmento
Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620648/effect-of-fc-%C3%AE-receptor-polymorphism-on-rituximab-mediated-b-cell-depletion-in-abo-incompatible-adult-living-donor-liver-transplantation
#12
Hiroshi Sakai, Yuka Tanaka, Hirofumi Tazawa, Seiichi Shimizu, Sapana Verma, Masahiro Ohira, Hiroyuki Tahara, Kentaro Ide, Kohei Ishiyama, Tsuyoshi Kobayashi, Takashi Onoe, Hideki Ohdan
BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS: SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#13
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28620050/engineering-the-fragment-crystallizable-fc-region-of-human-igg1-multimers-and-monomers-to-fine-tune-interactions-with-sialic-acid-dependent-receptors
#14
Patricia A Blundell, Ngoc Phuong Lan Le, Joel Allen, Yasunori Watanabe, Richard J Pleass
Multimeric fragment crystallizable (Fc) regions and Fc-fusion proteins are actively being explored as biomimetic replacements for intravenous immunoglobulin (IVIG) therapy, which is deployed to manage many diseases and conditions but is expensive and not always efficient. The Fc region of human IgG1 (IgG1-Fc) can be engineered into multimeric structures (hexa-Fcs) that bind their cognate receptors with high avidity. The critical influence of the unique N-linked glycan attached at Asn-297 on the structure and function of IgG1-Fc is well documented; however, whether the N-linked glycan has a similarly critical role in multimeric, avidly binding Fcs is unknown...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28617559/blockade-of-il-17-alleviated-inflammation-in-rat-arthritis-and-mmp-13-expression
#15
X-L Shui, W Lin, C-W Mao, Y-Z Feng, J-Z Kong, S-M Chen
OBJECTIVE: Rheumatoid arthritis (RA) is one systemic auto-immune disorder featured as chronic synovitis and can destruct joint cartilage. Fibroblast-like synoviocyte (FLS) secretes various factors affecting chondrocyte matrix and degradation. This study thus investigated the effect of interleukin-17A (IL-17A) on FLS and osteoclast. MATERIALS AND METHODS: Type II collagen-induced arthritis (CIA) rats were assigned to CIA model, CIA + IgG1 isotype, and CIA + Anti-Rat IL-17A groups...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#16
Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT...
May 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28615123/quantification-of-equine-immunoglobulin-a-in-serum-and-secretions-by-a-fluorescent-bead-based-assay
#17
Christiane L Schnabel, Susanna Babasyan, Heather Freer, Bettina Wagner
Only few quantitative reports exist about the concentrations and induction of immunoglobulin A (IgA) in mucosal secretions of horses. Despite this, it is widely assumed that IgA is the predominant immunoglobulin on mucosal surfaces in the horse. Here, two new monoclonal antibodies (mAbs) against equine IgA, clones 84-1 and 161-1, were developed and characterized in detail. Both IgA mAbs specifically bound monomeric and dimeric equine IgA in different applications, such as Western blots and fluorescent bead-based assays...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28614662/investigating-liquid-liquid-phase-separation-of-a-monoclonal-antibody-using-solution-state-nmr-spectroscopy-effect-of-arg%C3%A2-glu-and-arg%C3%A2-hcl
#18
Priscilla Kheddo, Jack E Bramham, Rebecca J Dearman, Shahid Uddin, Christopher F van der Walle, Alexander P Golovanov
Liquid-liquid phase separation (LLPS) of monoclonal antibody (mAb) formulations involves spontaneous separation into dense (protein-rich) and diluted (protein-lean) phases, and should be avoided in the final drug product. Understanding the factors leading to LLPS, and ways to predict and prevent it would therefore be highly beneficial. Here we describe the link between LLPS behavior of an IgG1 mAb ('mAb5'), its solubility and parameters extracted using (1)H NMR spectroscopy, for various formulations. We show that the formulations demonstrating least LLPS lead to the largest mAb5 NMR signal intensities...
June 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28613137/measurement-of-the-igg2-response-to-pneumococcal-capsular-polysaccharides-may-identify-an-antibody-deficiency-in-individuals-referred-for-immunological-investigation
#19
Antony Parker, Juan Irure Ventura, Dawn Sims, Ainara Echeverría de Carlos, Ricardo Gómez de la Torre, Lourdes Tricas Aizpún, J Gonzalo Ocejo-Vinyals, Marcos López-Hoyos, Gregg Wallis, Stephen Harding
IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs 29.5mg/L, 95% CI 13.5-90, p=0...
June 14, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28606183/allergenic-activity-of-pseudoterranova-decipiens-nematoda-anisakidae-in-balb-c-mice
#20
Alessandra Ludovisi, Gabriella Di Felice, Noelia Carballeda-Sangiao, Bianca Barletta, Cinzia Butteroni, Silvia Corinti, Gianluca Marucci, Miguel González-Muñoz, Edoardo Pozio, Maria Angeles Gómez-Morales
BACKGROUND: Anisakis simplex is the only fishery-product associated parasite causing clinical allergic responses in humans so far. However, other anisakids, due to the presence of shared or own allergens, could also lead to allergic reactions after sensitization. The aim of this study was to determine if Pseudoterranova decipiens belonging to the family Anisakidae has allergenic activity and is able to induce sensitization after oral administration in a murine (BALB/c mice) model. RESULTS: The ingestion of A...
June 12, 2017: Parasites & Vectors
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