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https://www.readbyqxmd.com/read/28811589/patients-with-igg1-anti-red-blood-cell-autoantibodies-show-aberrant-fc-glycosylation
#1
Myrthe E Sonneveld, Masja de Haas, Carolien Koeleman, Noortje de Haan, Sacha S Zeerleder, Peter C Ligthart, Manfred Wuhrer, C Ellen van der Schoot, Gestur Vidarsson
Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810902/the-isotype-and-igg-subclass-distribution-of-anti-carbamylated-protein-antibodies-in-rheumatoid-arthritis-patients
#2
Myrthe A M van Delft, Marije K Verheul, Leonie E Burgers, Veerle F A M Derksen, Annette H M van der Helm-van Mil, Diane van der Woude, Tom W J Huizinga, René E M Toes, Leendert A Trouw
BACKGROUND: Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28810661/identification-of-lectin-counter-receptors-on-cell-membranes-by-proximity-labeling
#3
Gang Wu, Manjula Nagala, Paul R Crocker
Lectin-glycan interactions play important roles in many biological systems, but the nature of glycoprotein counter-receptors expressed on cell membranes is often poorly understood. To help overcome this problem, we developed a method based on proximity labeling technology. Using a peroxidase-coupled lectin, addition of H2O2 and tyramide-biotin substrates leads to generation of short-range biotin radicals that biotinylate proteins in the immediate vicinity of the bound lectin, which can subsequently be identified...
September 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28805498/gingiskhan%C3%A2-protease-cleavage-allows-a-high-throughput-antibody-to-fab-conversion-enabling-direct-functional-assessment-during-lead-identification-of-human-monoclonal-and-bispecific-igg1-antibodies
#4
Jörg Moelleken, Manuel Endesfelder, Christian Gassner, Sabine Lingke, Simone Tomaschek, Oksana Tyshchuk, Stefan Lorenz, Ulrike Reiff, Michael Mølhøj
The determination of the binding strength of immunoglobulins (IgGs) to targets can be influenced by avidity when the targets are soluble di- or multimeric proteins, or associated to cell surfaces, including surfaces introduced from heterogeneous assays. However, for the understanding of the contribution of a second drug-to-target binding site in molecular design, or for ranking of monovalent binders during lead identification, affinity-based assessment of the binding strength is required. Typically, monovalent binders like antigen-binding fragments (Fabs) are generated by proteolytic cleavage with papain, which often results in a combination of under- and over-digestion, and requires specific optimization and chromatographic purification of the desired Fabs...
August 14, 2017: MAbs
https://www.readbyqxmd.com/read/28805137/differential-influences-of-fc-gamma-receptor-blocking-on-the-effects-of-certolizumab-pegol-and-infliximab-on-human-monocytes
#5
Takayuki Hoshiyama, Yu Matsueda, Toshihiro Tono, Yoshiyuki Arinuma, Tatsuo Nagai, Shunsei Hirohata
OBJECTIVES: To compare the effects of certolizumab pegol (CZP) and infliximab (IFX) on human monocytes. METHODS: Highly purified monocytes from healthy donors were cultured with CZP, IFX, control IgG1, or polyethylene glycol (PEG) at pharmacological attainable concentrations in culture medium with 10% autologous normal human serum (NHS) or with fetal bovine serum (FBS) for 24 h, after which the supernatants were replaced by fresh culture medium containing LPS...
August 14, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28802755/pneumococcal-conjugate-vaccination-response-in-patients-after-community-acquired-pneumonia-differences-in-patients-with-s-pneumoniae-versus-other-pathogens
#6
G H J Wagenvoort, B J M Vlaminckx, D A van Kessel, R C L Geever, B A W de Jong, J C Grutters, W J W Bos, B Meek, G T Rijkers
OBJECTIVES: The goal of this study is to investigate the immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in former pneumococcal CAP patients. We hypothesize that an impaired or suboptimal humoral immune response against (specific) pneumococcal serotypes might explain the vulnerability for pneumococcal disease. METHODS: Hospitalised adult CAP patients who participated in two trials (2004-2006 (n=201) and, 2007-2009 (n=304)) were screened. Patients eligible for inclusion had CAP caused by either S...
August 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28802255/simultaneous-targeting-of-two-distinct-epitopes-on-met-effectively-inhibits-met-and-hgf-driven-tumor-growth-by-multiple-mechanisms
#7
Michael M Grandal, Serhiy Havrylov, Thomas Tuxen Poulsen, Klaus Koefoed, Anna Dahlman, Gunther R Galler, Paolo Conrotto, Sara Collins, Karsten W Eriksen, Dafna Kaufman, George F Vande Woude, Helle J Jacobsen, Ivan D Horak, Michael Kragh, Johan Lantto, Thomas Bouquin, Morag Park, Mikkel Wandahl Pedersen
Increased MET activity is linked with poor prognosis and outcome in several human cancers currently lacking targeted therapies. Here we report on the characterization of Sym015, an antibody mixture composed of two humanized IgG1 antibodies against non-overlapping epitopes of MET. Sym015 was selected by high-throughput screening searching for antibody mixtures with superior growth inhibitory activity against MET-dependent cell lines. Synergistic inhibitory activity of the antibodies comprising Sym015 was observed in several cancer cell lines harboring amplified MET locus and was confirmed in vivo Sym015 was found to exert its activity via multiple mechanisms...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28802126/derp1-modified-dendritic-cells-attenuate-allergic-inflammation-by-regulating-the-development-of-t-helper-type1-th1-th2-cells-and-regulatory-t-cells-in-a-murine-model-of-allergic-rhinitis
#8
Shaoqing Yu, Bing Han, Shuangxi Liu, Hong Wang, Wenjie Zhuang, Yu Huang, Ruxin Zhang
The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR)...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28802077/helicobacter-pylori-and-its-secreted-immunomodulator-vaca-protect-against-anaphylaxis-in-experimental-models-of-food-allergy
#9
Andreas Kyburz, Sabine Urban, Aleksandra Altobelli, Stefan Floess, Jochen Huehn, Timothy L Cover, Anne Müller
BACKGROUND: Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium Helicobacter pylori. OBJECTIVE: The objective of this work was to investigate whether experimental infection with H. pylori, or prophylactic treatment with H. pylori-derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively...
August 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28801554/delayed-fractional-dose-regimen-of-the-rts-s-as01-malaria-vaccine-candidate-enhances-an-igg4-response-that-inhibits-serum-opsonophagocytosis
#10
Sidhartha Chaudhury, Jason A Regules, Christian A Darko, Sheetij Dutta, Anders Wallqvist, Norman C Waters, Erik Jongert, Franck Lemiale, Elke S Bergmann-Leitner
A recent study of the RTS,S malaria vaccine, which is based on the circumsporozoite protein (CSP), demonstrated an increase in efficacy from 50-60% to 80% when using a delayed fractional dose regimen, in which the standard 0-1-2 month immunization schedule was modified to a 0-1-7 month schedule and the third immunization was delivered at 20% of the full dose. Given the role that antibodies can play in RTS,S-induced protection, we sought to determine how the modified regimen alters IgG subclasses and serum opsonophagocytic activity (OPA)...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800475/biological-immunological-and-functional-properties-of-two-novel-multi-variant-chimeric-recombinant-proteins-of-csp-antigens-for-vaccine-development-against-plasmodium-vivax-infection
#11
Samaneh H Shabani, Sedigheh Zakeri, Ali H Salmanian, Jafar Amani, Akram A Mehrizi, Georges Snounou, François Nosten, Chiara Andolina, Yousef Mourtazavi, Navid D Djadid
The circumsporozoite protein (CSP) of the malaria parasite Plasmodium vivax is a major pre-erythrocyte vaccine candidate. The protein has a central repeat region that belongs to one of repeat families (VK210, VK247, and the P. vivax-like). In the present study, computer modelling was employed to select chimeric proteins, comprising the conserved regions and different arrangements of the repeat elements (VK210 and VK247), whose structure is similar to that of the native counterparts. DNA encoding the selected chimeras (named CS127 and CS712) were synthetically constructed based on E...
August 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28798366/elevated-serum-antibody-against-schistosoma-japonicum-hsp60-as-a-promising-biomarker-for-liver-pathology-in-schistosomiasis
#12
Xiaojun Chen, Wei Li, Yalin Li, Lei Xu, Sha Zhou, Jifeng Zhu, Zhipeng Xu, Feng Liu, Dandan Lin, Fei Hu, Yuemin Liu, Wen Jiang, Liwang Cui, Chuan Su
The pathology associated with Schistosoma japonicum (S. japonicum) infection in humans is attributed to parasite egg-induced granulomatous inflammation and fibrosis in the host liver. Currently, a marker that is reliable, cheap, less device-dependent, and can be easily and repeatedly used on a large scale to monitor the progression of liver pathology in schistosomiasis japonica endemic areas is lacking. The levels of serum S. japonicum heat shock protein 60 (SjHSP60)-specific IgG and its subtype antibodies in animals (mice and rabbits) or patients with schistosomiasis were measured by ELISA...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796897/hookworm-excretory-secretory-products-modulate-immune-responses-to-heterologous-and-species-specific-antigens
#13
Nicholas Diliani, Blaise Dondji
Approximately one billion people are currently infected with hookworm. Despite its high prevalence and the concomitant immune suppression seen in infected individuals, little research has been done on the mechanism of immunosuppression by hookworm. Our study focused on characterizing mechanisms utilized by hookworm to suppress the host immune response. Splenocytes and draining lymph node cells from mice injected with hookworm excretory/secretory (ES) proteins showed decreased proliferation in response to both heterologous and species-specific antigens while also having increased nitric oxide secretion...
August 10, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28793911/igg-fc-galactosylation-predicts-response-to-methotrexate-in-early-rheumatoid-arthritis
#14
Susanna L Lundström, Aase H Hensvold, Dorothea Rutishauser, Lars Klareskog, A Jimmy Ytterberg, Roman A Zubarev, Anca I Catrina
BACKGROUND: Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that is difficult to predict. The glycosylation status of immunoglobulin G (IgG) is altered in RA and influenced by MTX treatment. We aimed to further investigate if IgG glycosylation in untreated early RA can predict therapeutic response to MTX. METHODS: We used a shotgun proteomic approach to screen for the Fc glycopeptides in the serum of 12 control subjects and 59 untreated patients with early RA prior to and following MTX initiation...
August 9, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28791259/toxoplasma-co-infection-prevents-th2-differentiation-and-leads-to-a-helminth-specific-th1-response
#15
Norus Ahmed, Timothy French, Sebastian Rausch, Anja Kühl, Katrin Hemminger, Ildiko R Dunay, Svenja Steinfelder, Susanne Hartmann
Nematode infections, in particular gastrointestinal nematodes, are widespread and co-infections with other parasites and pathogens are frequently encountered in humans and animals. To decipher the immunological effects of a widespread protozoan infection on the anti-helminth immune response we studied a co-infection with the enteric nematode Heligmosomoides polygyrus in mice previously infected with Toxoplasma gondii. Protective immune responses against nematodes are dependent on parasite-specific Th2 responses associated with IL-4, IL-5, IL-13, IgE, and IgG1 antibodies...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28789852/recombinant-calponin-of-human-filariid-brugia-malayi-secondary-structure-and-immunoprophylactic-potential
#16
Shiv K Verma, Ashish Arora, P Kalpana Murthy
In the search for potential vaccine candidates for the control of human lymphatic filariasis, we recently identified calponin-like protein, that regulates actin/myosin interactions, in a proinflammatory fraction F8 (45.24-48.64kDa) of Brugia malayi adult worms. In the present study, the gene was cloned, expressed, and the recombinant Calponin of B. malayi (r-ClpBm) was prepared and characterized. r-ClpBm bears homology with OV9M of Onchocerca volvulus, a non-lymphatic filariid that causes loss of vision and cutaneous pathology...
August 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28782655/on-the-role-of-igg4-in-inflammatory-conditions-lessons-for-igg4-related-disease
#17
REVIEW
David C Trampert, Lowiek M Hubers, Stan F J van de Graaf, Ulrich Beuers
The pathophysiology of immunoglobulin G4-related disease (IgG4-RD) and its most common manifestations, IgG4-associated (sclerosing) cholangitis and autoimmune pancreatitis, remains largely unknown, but IgG4 is presumably involved. IgG4 is a promiscuous antibody, which could be directly pathogenic, fulfill a protective role, or could just be a fortuitous marker of an aberrant inflammatory response. IgG4 antibodies possess exclusive structural and functional characteristics suggesting anti-inflammatory and tolerance-inducing effects...
August 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28780374/maternal-t-and-b-cell-engraftment-in-two-cases-of-x-linked-severe-combined-immunodeficiency-with-igg1-gammopathy
#18
Tsubasa Okano, Takuro Nishikawa, Eri Watanabe, Takashi Watanabe, Takehiro Takashima, Tzu-Wen Yeh, Motoi Yamashita, Mari Tanaka-Kubota, Satoshi Miyamoto, Noriko Mitsuiki, Masatoshi Takagi, Yoshifumi Kawano, Yoshiki Mochizuki, Kohsuke Imai, Hirokazu Kanegane, Tomohiro Morio
X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Exclusively, maternal B cells were found among the IgD(-)CD27(+) class-switched memory B cells, whereas the patients' B cells remained naïve...
August 2, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28777260/persistence-of-parenchymal-and-perivascular-t-cells-in-treatment-refractory-anti-n-methyl-d-aspartate-receptor-encephalitis
#19
Alexander Filatenkov, Timothy E Richardson, Elena Daoud, Sarah F Johnson-Welch, Denise M Ramirez, Jose Torrealba, Benjamin Greenberg, Nancy L Monson, Veena Rajaram
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease mediated by IgG1 or IgG3 antibodies to the GluN1 subunit of the NMDAR, resulting in downregulation of NMDARs. Early diagnosis, prompt reduction of anti-NMDAR antibodies, and removal of associated ovarian tumors when identified are important drivers of prognosis. Immunohistochemical studies were carried out to evaluate B cell, plasma cell, and T-cell infiltrates in the brain of a 3-year-old patient with anti-NMDAR encephalitis who failed to show improvement after plasma exchange and Rituximab treatment...
August 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28777067/schistosoma-mansoni-cercarial-elastase-smce-differences-in-immunogenic-properties-of-native-and-recombinant-forms
#20
Marwa H El-Faham, Katherine J Wheatcroft-Francklow, Helen P Price, Jon R Sayers, Michael J Doenhoff
The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude preparations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum glutathione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization...
September 2017: Parasitology
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