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https://www.readbyqxmd.com/read/28542406/human-igg3-with-extended-half-life-does-not-improve-fc-gamma-receptor-mediated-cancer-antibody-therapies-in-mice
#1
Rens Braster, Simran Grewal, Remco Visser, Helga K Einarsdottir, Marjolein van Egmond, Gestur Vidarsson, Marijn Bögels
BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models...
2017: PloS One
https://www.readbyqxmd.com/read/28515723/different-somatic-hypermutation-levels-among-antibody-subclasses-disclosed-by-a-new-next-generation-sequencing-based-antibody-repertoire-analysis
#2
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
#3
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
#4
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/28463043/affinity-of-human-igg-subclasses-to-mouse-fc-gamma-receptors
#5
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/28459117/the-human-thymus-perivascular-space-is-a-functional-niche-for-viral-specific-plasma-cells
#6
Sarah Nuñez, Carolina Moore, Baoshan Gao, Kortney Rogers, Yessia Hidalgo, Pedro J Del Nido, Susan Restaino, Yoshifumi Naka, Govind Bhagat, Joren C Madsen, María Rosa Bono, Emmanuel Zorn
The human thymus is susceptible to viral infections that can severely alter thymopoiesis and compromise the mechanisms of acquired tolerance to self-antigens. In humans, plasma cells residing primarily in the bone marrow confer long-lasting protection to common viruses by secreting antigen-specific antibodies. Since the thymus also houses B cells, we examined the phenotypic complexity of these thymic resident cells and their possible protective role against viral infections. Using tissue specimens collected from subjects ranging in age from 5 days to 71 years, we found that starting during the first year of life, CD138(+) plasma cells (PC) begin accumulating in the thymic perivascular space (PVS) where they constitutively produce IgG without the need for additional stimulation...
December 2016: Science Immunology
https://www.readbyqxmd.com/read/28459012/stage-specific-antibody-response-against-two-larval-stages-of-brugia-malayi-in-different-clinical-spectra-of-brugian-filariasis
#7
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
https://www.readbyqxmd.com/read/28457528/disease-associations-with-isolated-elevations-of-each-of-the-four-igg-subclasses
#8
Sarah Engelhart, Robert J Glynn, Peter H Schur
PURPOSE: Immunoglobulin G4-related disease (IgG4-RD) is a relatively newly defined disease entity that refers to a group of immune-mediated disorders that have certain histopathologic, serologic, and clinical features in common. IgG4-RD is often associated with elevated serum IgG4. The discovery of IgG4-RD highlights the scarcity of literature examining elevations in other IgG subclasses and their potential associations to disease. In this retrospective chart review study, we aim to address that gap, by exploring disease associations in patients with isolated IgG subclass elevations...
March 30, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28449462/pulmonary-function-tests-findings-and-their-diagnostic-value-in-patients-with-igg4-related-disease
#9
Lu Cao, Yi-Bing Chen, Da-Hui Zhao, Wen-Fang Shi, Song Meng, Li-Xin Xie
BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect most organs. To date, there have been no detailed assessments of pulmonary function in patients with IgG4-RD. In this study, we investigated pulmonary function in IgG4-RD patients and evaluated the value of pulmonary function tests (PFTs) in diagnosing IgG4-related respiratory disease (IgG4-RRD). METHODS: This was a retrospective study of 17 patients with IgG4-RD...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#10
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28444306/immunoglobulin-based-investigation-of-spontaneous-resolution-of-chlamydia-trachomatis-infection
#11
Rakesh Bakshi, Kanupriya Gupta, Stephen J Jordan, LaDraka' T Brown, Christen G Press, Rachel J Gorwitz, John R Papp, Sandra G Morrison, Jeannette Y Lee, Richard P Morrison, William M Geisler
Chlamydia trachomatis (CT) elementary body (EB) ELISA was used to investigate serum anti-CT IgG1 (long-lived response) and IgG3 (short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. 71.4% of women were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3- at both visits, suggesting absence of recent chlamydia. Using EB ELISA, we demonstrated about one in six women classified as having spontaneous resolution of chlamydia might have been exposed to CT but not infected...
April 21, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28422752/t-bet-b-cells-are-induced-by-human-viral-infections-and-dominate-the-hiv-gp140-response
#12
James J Knox, Marcus Buggert, Lela Kardava, Kelly E Seaton, Michael A Eller, David H Canaday, Merlin L Robb, Mario A Ostrowski, Steven G Deeks, Mark K Slifka, Georgia D Tomaras, Susan Moir, M Anthony Moody, Michael R Betts
Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28418769/persistency-of-neutralizing-anti-interferon-%C3%AE-antibodies-in-patients-with-multiple-sclerosis-treated-with-subcutaneous-interferon-%C3%AE-depends-on-antibody-titers-igg-subclasses-and-affinity-maturation
#13
Irena Dujmovic, Harald Hegen, Pedro Paz, Ed Croze, Florian Deisenhammer
Neutralizing antibodies may affect interferon (IFN)-β treatment efficacy, but mechanisms of neutralizing anti-drug antibody (ADA) evolution are not fully elucidated. We investigated the relationship between ADA titers, IgG subclass profile, and binding affinity with the development and persistency of neutralizing ADA in relapsing-remitting multiple sclerosis (MS) patients treated with subcutaneous IFN-β. A total of 94 patients, who had blood sampling at months 6, 12, 24, and 36 during IFN-β therapy, were included into this retrospective study and stratified to the following: non-neutralizing, transient, and persistent neutralizing ADA status...
April 18, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28364500/antibodies-against-hypocretin-receptor-2-are-rare-in-narcolepsy
#14
Maria Pia Giannoccaro, Patrick Waters, Fabio Pizza, Rocco Liguori, Giuseppe Plazzi, Angela Vincent
Study Objectives: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Methods: Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied...
February 1, 2017: Sleep
https://www.readbyqxmd.com/read/28359755/a-novel-staphylococcal-enterotoxin-b-subunit-vaccine-candidate-elicits-protective-immune-response-in-a-mouse-model
#15
Jun Young Choi, Sungho Shin, Na Young Kim, Woo Sung Son, Tae Jin Kang, Dong Hyun Song, Chi Ho Yu, Gyeung Haeng Hur, Seong Tae Jeong, Young Kee Shin
Staphylococcal enterotoxin B (SEB), produced by the gram-positive bacterium Staphylococcus aureus, is responsible for food poisoning and toxic shock syndrome, and is considered a potential bioterrorism agent. Unfortunately, still now no approved vaccines are available against SEB. In this study, we constructed a series of nontoxic SEB mutants (mSEBs) and examined whether these mSEBs provide protective immunity against SEB challenge. These mSEB vaccine candidates did not demonstrate superantigen activity in mouse splenocyte cultures...
March 27, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28351925/serum-igg2-and-tissue-igg2-plasma-cell-elevation-in-orbital-igg4-related-disease-igg4-rd-potential-use-in-igg4-rd-assessment
#16
Anita S Y Chan, Hardeep Mudhar, Sunny Yu Shen, Stephanie S Lang, Malee Fernando, Maryam Hazly Hilmy, Naomi Jayne Guppy, Ian Rennie, Lisa Dunkley, Issam Al Jajeh
AIMS: To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. METHODS: This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016...
March 28, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28334051/dissecting-the-relationships-of-igg-subclasses-and-complements-in-membranous-lupus-nephritis-and-idiopathic-membranous-nephropathy
#17
Woong Na, Kijong Yi, Young Soo Song, Moon Hyang Park
Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks...
2017: PloS One
https://www.readbyqxmd.com/read/28329101/naturally-acquired-antibodies-target-the-glutamate-rich-protein-on-intact-merozoites-and-predict-protection-against-febrile-malaria
#18
Ikhlaq Hussain Kana, Bright Adu, Régis Wendpayangde Tiendrebeogo, Susheel Kumar Singh, Daniel Dodoo, Michael Theisen
Background.: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies. Methods.: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay...
February 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28325049/antibody-subclass-detection-using-graphene-nanopores
#19
Amir Barati Farimani, Mohammad Heiranian, Kyoungmin Min, Narayana R Aluru
Solid-state nanopores are promising for label-free protein detection. The large thickness, ranging from several tens of nanometers to micrometers and larger, of solid-state nanopores prohibits atomic-scale scanning or interrogation of proteins. Here, a single-atom thick graphene nanopore is shown to be highly capable of sensing and discriminating between different subclasses of IgG antibodies despite their minor and subtle variation in atomic structure. Extensive molecular dynamics (MD) simulations, rigorous statistical analysis with a total aggregate simulation time of 2...
March 28, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28315348/fc-gamma-receptor-3a-polymorphism-predicts-the-incidence-of-urinary-tract-infection-in-kidney-transplant-recipients
#20
Lalit Kumar Das, Kentaro Ide, Asuka Tanaka, Hiroshi Morimoto, Seiichi Shimizu, Naoki Tanimine, Yuka Tanaka, Hideki Ohdan
We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after kidney transplantation (KT). The single-nucleotide polymorphisms (SNPs) of C1QA [276 A/G], FCGR2A [131 H/R], and FCGR3A [158 F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 81 KT recipients in relation to the occurrences of postoperative infectious complications within 30days after KT. Consistent with a lower affinity of the isoform encoded by the FCGR3A [158 F] to both IgG1 and IgG3, a significantly higher incidence of urinary tract infections (UTIs) was observed in the FCGR3A [158 F/V or F/F] individuals (65...
April 2017: Human Immunology
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