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https://www.readbyqxmd.com/read/28634480/fc-galactosylation-of-human-immunoglobulin-gamma-isotypes-improves-c1q-binding-and-enhances-complement-dependent-cytotoxicity
#1
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/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#2
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#3
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/28613137/measurement-of-the-igg2-response-to-pneumococcal-capsular-polysaccharides-may-identify-an-antibody-deficiency-in-individuals-referred-for-immunological-investigation
#4
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/28606325/quantification-of-anti-leishmania-antibodies-in-saliva-of-dogs
#5
Ana Cantos-Barreda, Damián Escribano, Luis J Bernal, José J Cerón, Silvia Martínez-Subiela
Detection of serum anti-Leishmania antibodies by quantitative or qualitative techniques has been the most used method to diagnose Canine Leishmaniosis (CanL). Nevertheless, saliva may represent an alternative to blood because it is easy to collect, painless and non-invasive in comparison with serum. In this study, two time-resolved immunofluorometric assays (TR-IFMAs) for quantification of anti-Leishmania IgG2 and IgA antibodies in saliva were developed and validated and their ability to distinguish Leishmania-seronegative from seropositive dogs was evaluated...
August 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28604502/the-association-of-hiv-1-gag-specific-igg-antibodies-with-natural-control-of-hiv-1-infection-in-individuals-not-carrying-hla-b-57-01-is-only-observed-in-viremic-controllers
#6
M Christian Tjiam, Mazmah A Morshidi, Lucy Sariputra, Jeffrey N Martin, Steven G Deeks, Dino Tan, Silvia Lee, Sonia Fernandez, Martyn A French
To expand upon our previous observation that HIV-1 Gag-specific IgG antibodies were highest in HIV controllers not carrying HLA-B*57:01, we analysed these antibodies in a larger cohort of viremic controllers (VCs) or elite controllers (ECs) considering carriage of 'protective' HLA-B alleles. HIV-1 p24-specific IgG1 and IgG2 antibodies were higher only in HLA-B*57:01 VCs but there were no differences in ECs. Associations of HIV-1 gp140-specific IgG antibodies with HLA-B*57:01 carriage were inconsistent amongst VCs and ECs...
June 9, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28601035/effects-of-dietary-cla-supplementation-parity-and-different-concentrate-levels-before-calving-on-immunoglobulin-g1-g2-and-m-concentrations-in-dairy-cows
#7
Melanie Eger, Jana Horn, Jamal Hussen, Hans-Joachim Schuberth, Maria Scharf, Ulrich Meyer, Sven Dänicke, Hartwig Bostedt, Gerhard Breves
Peripartal dairy cows exhibit a higher susceptibility for infectious diseases, which might be linked to the negative energy balance occurring at the onset of lactation. A dietary supplementation of conjugated linoleic acids (CLA) may reduce milk fat yield and subsequently lower the energy deficit. The utilization of immunoglobulins (Ig) for colostrogenesis might impair humoral immunity in peripartal dairy cows; therefore this study investigated the effects of a CLA supplement, parity and different dietary energy levels on plasma and colostrum IgG1, IgG2 and IgM levels in dairy cows and their calves...
June 2, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28585289/effects-of-weak-non-complement-binding-hla-antibodies-on-c1q-binding
#8
G Hönger, P Amico, M-L Arnold, B M Spriewald, S Schaub
It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding...
June 5, 2017: HLA
https://www.readbyqxmd.com/read/28580661/b-lymphocytes-repress-hepatic-tumorigenesis-but-not-development-in-hras12v-transgenic-mice
#9
Kangwei Wang, Xin Nie, Zhuona Rong, Tingting Fan, Juan Li, Xinxin Wang, Huiling Li, Jianyi Dong, Jun Chen, Fujin Wang, Jingyu Wang, Aiguo Wang
Increasing reports show noninflammation underlying HCC, challenging our understanding of the roles of the immune system in hepatocarcinogenesis. By exploring a mouse model of hepatic tumor induced by hepatocyte-specific expression of the Hras12V oncogene without obvious inflammation, we found that the proportion of B cells, but not T cells, progressively and significantly decreased in 3, 5-month-old transgenic mice (Tg) compared with non-transgenic mice. Notably, the proportions of total and activated B and T cells all significantly decreased in 9-month-old Tg with multiple massive hepatic tumors...
June 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28570837/high-throughput-screening-and-analysis-of-charge-variants-of-monoclonal-antibodies-in-multiple-formulations
#10
Larysa Alekseychyk, Cheng Su, Gerald W Becker, Michael J Treuheit, Vladimir I Razinkov
Among different biopharmaceutical products, monoclonal antibodies (mAbs) show a high level of complexity, including heterogeneity due to differences in size, hydrophobicity, charge, and so forth. Such heterogeneity can be related to both cell-based production and any of the stages of purification, storage, and delivery that the mAb is subjected to. Choosing the right formulation composition providing both physical and chemical stabilities can be a very challenging process, especially when done in the limited time frame required for a typical drug development cycle...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28566370/enhanced-effector-functions-due-to-antibody-defucosylation-depend-on-the-effector-cell-fc%C3%AE-receptor-profile
#11
Christine W Bruggeman, Gillian Dekkers, Arthur E H Bentlage, Louise W Treffers, Sietse Q Nagelkerke, Suzanne Lissenberg-Thunnissen, Carolien A M Koeleman, Manfred Wuhrer, Timo K van den Berg, Theo Rispens, Gestur Vidarsson, Taco W Kuijpers
Abs of the IgG isotype are glycosylated in their Fc domain at a conserved asparagine at position 297. Removal of the core fucose of this glycan greatly increases the affinity for FcγRIII, resulting in enhanced FcγRIII-mediated effector functions. Normal plasma IgG contains ∼94% fucosylated Abs, but alloantibodies against, for example, Rhesus D (RhD) and platelet Ags frequently have reduced fucosylation that enhances their pathogenicity. The increased FcγRIII-mediated effector functions have been put to use in various afucosylated therapeutic Abs in anticancer treatment...
May 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28546550/human-igg2-and-igg4-expressing-memory-b-cells-display-enhanced-molecular-and-phenotypic-signs-of-maturity-and-accumulate-with-age
#12
Britt G de Jong, Hanna IJspeert, Lemelinda Marques, Mirjam van der Burg, Jacques J M van Dongen, Bruno G Loos, Menno C van Zelm
The mechanisms involved in sequential immunoglobulin (IG)G class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on PBMC from young children and adults as models for primary and secondary immunological memory...
May 26, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28532483/naturally-acquired-humoral-and-cellular-immune-responses-to-plasmodium-vivax-merozoite-surface-protein-8-in-patients-with-p-vivax-infection
#13
Yang Cheng, Bo Wang, Siriruk Changrob, Jin-Hee Han, Jetsumon Sattabongkot, Kwon-Soo Ha, Patchanee Chootong, Feng Lu, Jun Cao, Myat Htut Nyunt, Won Sun Park, Seok-Ho Hong, Chae Seung Lim, Takafumi Tsuboi, Eun-Taek Han
BACKGROUND: Thirty-one glycosylphosphatidylinositol (GPI)-anchored proteins of Plasmodium vivax, merozoite surface protein 1 (MSP1), MSP1 paralogue, MSP4, MSP5, MSP8, and MSP10 have been reported from homologs of Plasmodium falciparum by gene annotation with bioinformatics tools. These GPI-anchored proteins contain two epidermal growth factor (EGF)-like domains at its C-terminus. Here, P. vivax merozoite surface protein 8 (PvMSP8) are considered as potential targets of protective immunity...
May 22, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28515723/different-somatic-hypermutation-levels-among-antibody-subclasses-disclosed-by-a-new-next-generation-sequencing-based-antibody-repertoire-analysis
#14
Kazutaka Kitaura, Hiroshi Yamashita, Hitomi Ayabe, Tadasu Shini, Takaji Matsutani, Ryuji Suzuki
A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28479893/igg-isotypic-antibodies-to-crude-plasmodium-falciparum-blood-stage-antigen-associated-with-placental-malaria-infection-in-parturient-cameroonian-women
#15
Judith K Anchang-Kimbi, Eric Akum Achidi, Blaise Nkegoum, Joseph-Marie N Mendimi, Eva Sverremark-Ekström, Marita Troye-Blomberg
BACKGROUND: Few studies have reported an association between placental malaria (PM) infection and levels of isotypic antibodies against non-pregnancy associated antigens. OBJECTIVE: To determine and evaluate IgG isotypic antibody levels to crude P. falciparum blood stage in women with and without PM infection. METHODS: Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen were measured by ELISA in 271 parturient women...
December 2016: African Health Sciences
https://www.readbyqxmd.com/read/28472610/nature-functions-and-clinical-implications-of-igg4-autoantibodies-in-systemic-lupus-erythematosus-and-rheumatoid-arthritis
#16
Qingjun Pan, Qiaofen Lan, Yanxia Peng, Jun Cai, Jian Zheng, Carol Dickerson, Haiyan Xiao, Hua-Feng Liu
Protective autoantibodies in homeostasis, clinical relevance, and therapeutic potential have gained wide attention. Recent studies showed that IgG4 autoantibodies play crucial roles in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In one aspect, IgG4 autoantibodies can bind autoantigens in competition with other classes of immunoglobulins (e.g., IgG1, IgG2a) to form non-inflammatory immune-complexes (ICs), which have a limited ability to induce immune responses because of the low affinity of IgG4 for both Fc receptors and the C1 complement molecule, resulting in reduced inflammatory response in SLE and RA...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28463977/production-of-igg-antibodies-to-pneumococcal-polysaccharides-is-associated-with-expansion-of-icos-circulating-memory-t-follicular-helper-cells-which-is-impaired-by-hiv-infection
#17
Laila N Abudulai, Sonia Fernandez, Karli Corscadden, Sally A Burrows, Michael Hunter, M Christian Tjiam, Lea-Ann S Kirkham, Jeffrey J Post, Martyn A French
Dysfunction of T follicular-helper (TFH) cells is a possible cause of impaired germinal centre (GC) and IgG antibody responses in individuals with human immunodeficiency virus-1 (HIV-1) infection and might contribute to decreased magnitude and isotype diversification of IgG antibodies to pneumococcal polysaccharides (PcPs). We examined the production of IgG1 and IgG2 antibodies to PcPs 4, 6B, 9V and 14 by enumerating antibody secreting cells (ASCs) at day (D) 7 and determining fold-increase in serum antibody levels at D28 after vaccination with unconjugated PcPs in HIV seronegative subjects (n = 20) and in HIV patients who were receiving antiretroviral therapy (ART) (n = 28) or who were ART-naive (n = 11) and determined their association with ICOS+ and ICOS- circulating memory TFH (cmTFH) cells (CD4+CD45RA-CD27+CXCR5+PD-1+) and short lived plasmablasts (SPBs) at D7, and with PcP-specific and total IgM+ and IgG+ memory B cells at D0...
2017: PloS One
https://www.readbyqxmd.com/read/28463043/affinity-of-human-igg-subclasses-to-mouse-fc-gamma-receptors
#18
Gillian Dekkers, Arthur E H Bentlage, Tamara C Stegmann, Heather L Howie, Suzanne Lissenberg-Thunnissen, James Zimring, Theo Rispens, Gestur Vidarsson
Human IgG is the main antibody class used in antibody therapies because of its efficacy and longer half-life, which are completely or partly due to FcγR-mediated functions of the molecules. Preclinical testing in mouse models are frequently performed using human IgG, but no detailed information on binding of human IgG to mouse FcγRs is available. The orthologous mouse and human FcγRs share roughly 60-70% identity, suggesting some incompatibility. Here, we report binding affinities of all mouse and human IgG subclasses to mouse FcγR...
May 2, 2017: MAbs
https://www.readbyqxmd.com/read/28460549/pharmacokinetic-drug-evaluation-of-brodalumab-for-the-treatment-of-psoriasis
#19
REVIEW
M Galluzzo, M Talamonti, S D'adamio, L Bianchi
Psoriasis is now understood to also be under the driving influence of the IL-17/IL-23 axis, and the medical breakthrough of novel IL-17 inhibitor medications signals a paradigm shift in the way psoriatic patients are managed medically. Brodalumab, a fully human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA monoclonal antibody, is currently the most-developed treatment that binds to the IL-17RA. The authors review and provide updates of efficacy and safety by several studies on brodalumab...
June 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28459012/stage-specific-antibody-response-against-two-larval-stages-of-brugia-malayi-in-different-clinical-spectra-of-brugian-filariasis
#20
Praveen Kumar Tripathi, Ramesh Chander Mahajan, Nancy Malla, Naveen Kumar, Shailja Misra Bhattacharya, Ranganatha Krishna Shinoy, Abhishek Mewara, Rakesh Sehgal
CONTEXT: T-cell hypo-responsiveness in microfilaria (Mf) carriers against the microfilarial stage antigen of Brugia malayi has been described, but no study has been carried out to assess antibody dynamics against stage-specific antigens. AIM: The work was carried out with the aim to assess stage-specific antibody responses against L3 and microfilarial stage antigens in brugian filariasis in an endemic area. SETTING AND DESIGN: Patients with different clinical spectra of brugian filariasis were recruited to evaluate antibody responses to brugian antigens...
January 2017: Tropical Parasitology
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