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antibody deficiency

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https://www.readbyqxmd.com/read/29150834/il-22-neutralizing-autoantibodies-impair-fungal-clearance-in-murine-oropharyngeal-candidiasis-model
#1
Rudolf Bichele, Jaanika Kärner, Kai Truusalu, Imbi Smidt, Reet Mändar, Heather R Conti, Sarah L Gaffen, Pärt Peterson, Martti Laan, Kai Kisand
Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29150289/the-cause-of-multiple-sclerosis-is-autoimmune-attack-of-adenosyltransferase-thereby-limiting-adenosylcobalamin-production
#2
J L Boucher
The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29142506/detection-of-circulating-natural-antibodies-to-inflammatory-cytokines-in-type-2-diabetes-and-clinical-significance
#3
Weiyi Cai, Cailing Qiu, Hongyu Zhang, Xiangyun Chen, Xuan Zhang, Qingyong Meng, Jun Wei
Background: Inflammatory cytokines have been demonstrated to be involved in developing insulin resistance and type-2 diabetes (T2D). Natural antibodies in the circulation have protective effects on common diseases in humans. The present study was thus designed to test the hypothesis that natural antibodies against inflammatory cytokines could be associated with T2D. Methods: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG against peptide antigens derived from interleukin 1α (IL1α), IL1β, IL6, IL8 and tumor necrosis factor-α (TNF-α) in 200 patients with T2D and 220 control subjects...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29142257/using-a-quantitative-quadruple-immunofluorescent-assay-to-diagnose-isolated-mitochondrial-complex-i-deficiency
#4
Syeda T Ahmed, Charlotte L Alston, Sila Hopton, Langping He, Iain P Hargreaves, Gavin Falkous, Monika Oláhová, Robert McFarland, Doug M Turnbull, Mariana C Rocha, Robert W Taylor
Isolated Complex I (CI) deficiency is the most commonly observed mitochondrial respiratory chain biochemical defect, affecting the largest OXPHOS component. CI is genetically heterogeneous; pathogenic variants affect one of 38 nuclear-encoded subunits, 7 mitochondrial DNA (mtDNA)-encoded subunits or 14 known CI assembly factors. The laboratory diagnosis relies on the spectrophotometric assay of enzyme activity in mitochondrially-enriched tissue homogenates, requiring at least 50 mg skeletal muscle, as there is no reliable histochemical method for assessing CI activity directly in tissue cryosections...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137040/a-multicenter-open-label-phase-iii-study-of-abcertin-in-gaucher-disease
#5
Beom Hee Lee, Ahmed Fathy Abdalla, Jin-Ho Choi, Amal El Beshlawy, Gu-Hwan Kim, Sun Hee Heo, Ahmed Megahed Hassan Megahed, Mona Abdel Latif Elsayed, Tarik El-Sayed Mohammad Barakat, Khaled Mohamed Abd El-Azim Eid, Mona Hassan El-Tagui, Mona Mohamed Hamdy Mahmoud, Ekram Fateen, June-Young Park, Han-Wook Yoo
BACKGROUND: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement. METHODS: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Each patient was administered a biweekly 60 U/kg dose of Abcertin for 6 months. The primary endpoint was the change in hemoglobin concentration. The secondary endpoints were changes from baseline in platelet counts, spleen and liver volumes, biomarker levels, skeletal parameters, and bone mineral density...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29133782/mtor-intersects-antibody-inducing-signals-from-taci-in-marginal-zone-b-cells
#6
Jordi Sintes, Maurizio Gentile, Shuling Zhang, Yolanda Garcia-Carmona, Giuliana Magri, Linda Cassis, Daniel Segura-Garzón, Alessandra Ciociola, Emilie K Grasset, Sabrina Bascones, Laura Comerma, Marc Pybus, David Lligé, Irene Puga, Cindy Gutzeit, Bing He, Wendy DuBois, Marta Crespo, Julio Pascual, Anna Mensa, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Sergi Serrano, Josep Lloreta, Eric Meffre, Michael Hahne, Charlotte Cunningham-Rundles, Beverly A Mock, Andrea Cerutti
Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29132376/ezh2-suppression-in-glioblastoma-shifts-microglia-toward-m1-phenotype-in-tumor-microenvironment
#7
Yatao Yin, Shuwei Qiu, Xiangpen Li, Bo Huang, Yun Xu, Ying Peng
BACKGROUND: Glioblastoma multiforme (GBM) induces tumor immunosuppression through interacting with tumor-infiltrating microglia or macrophages (TAMs) with an unclear pathogenesis. Enhancer of zeste homolog 2 (EZH2) is abundant in GBM samples and cell lines and is involved in GBM proliferation, cell cycle, and invasion, whereas its association with innate immune response is not yet reported. Herein, the aim of this study was to investigate the role of EZH2 in GBM immune. METHODS: Co-culturing models of human/murine GBM cells with PBMC-derived macrophages/primary microglia were employed...
November 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29130830/enhanced-cd103-expression-and-reduced-frequencies-of-virus-specific-cd8-t-cells-among-airway-lymphocytes-after-influenza-vaccination-of-mice-deficient-in-vitamins-a%C3%A2-%C3%A2-d
#8
Sherri L Surman, Bart G Jones, David L Woodland, Julia L Hurwitz
Previous research has evaluated antibody responses toward an influenza virus vaccine in the context of deficiencies for vitamins A and D (VAD+VDD). Results showed that antibodies and antibody-forming cells in the respiratory tract were reduced in VAD+VDD mice. However, effectors were recovered when oral supplements of vitamins A + D were delivered at the time of vaccination. Here we address the question of how vaccine-induced CD8(+) T cell responses are affected by deficiencies for vitamins A + D. VAD+VDD and control mice were vaccinated with an intranasal, cold-adapted influenza virus A/Puerto Rico/8/34 vaccine, with or without oral supplements of vitamins A + D...
November 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29130141/sj%C3%A3-gren-s-syndrome-initially-presented-as-thrombotic-thrombocytopenic-purpura-in-a-male-patient-a-case-report-and-literature-review
#9
REVIEW
Xiaohan Xu, Tienan Zhu, Di Wu, Lu Zhang
Thrombotic thrombocytopenic purpura (TTP) is a potentially lethal multisystem disorder which could be caused by autoimmune diseases. However, the concomitant occurrence of TTP and Sjögren's syndrome (SS) is an extremely uncommon scenario, especially in male patients. A 56-year-old Chinese male was admitted for the appearance of diffuse ecchymosis. Then he gradually developed transient slurred speech, progressive confusion, agitation, extremity weakness, and fever. Laboratory investigations suggested anemia, thrombocytopenia, significantly increased lactic dehydrogenase, schistocytes in peripheral blood smear, and a disintegrin-like metalloproteinase with thrombospondin motif type 1 member 13 (ADAMTS13) activity deficiency with high inhibitor titers...
November 13, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29128760/vitamin-d-deficiency-in-children-with-recurrent-respiratory-infections-with-or-without-immunoglobulin-deficiency
#10
Nel Dąbrowska-Leonik, Ewa Bernatowska, Małgorzata Pac, Wiktor Filipiuk, Jan Mulawka, Barbara Pietrucha, Edyta Heropolitańska-Pliszka, Katarzyna Bernat-Sitarz, Beata Wolska-Kuśnierz, Bożena Mikołuć
PURPOSE: The objective of this study was to evaluate thevitamin D concentration in patients with recurrent respiratory infections with or without immunoglobulin G, A or M (IgG, IgA, IgM) deficiency, and to find a correlation between the vitamin D concentration and the response to hepatitis B vaccination. MATERIALS AND METHOD: The study involved 730 patients with recurrent respiratory infections. The concentration of 25-hydroxyvitamin D (25(OH)D), immunoglobulins G, A and M, anti-HBs was determined...
November 9, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#11
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29126302/the-clinical-utility-of-measuring-igg-subclass-immunoglobulins-during-immunological-investigation-for-suspected-primary-antibody-deficiencies
#12
Antony R Parker, Markus Skold, David B Ramsden, J Gonzalo Ocejo-Vinyals, Marcos López-Hoyos, Stephen Harding
Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#13
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29124321/vaccine-responses-in-newborns
#14
REVIEW
Anja Saso, Beate Kampmann
Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants...
November 9, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29122947/phosphorylation-promotes-activation-induced-cytidine-deaminase-activity-at-the-myc-oncogene
#15
Yunxiang Mu, Monika A Zelazowska, Kevin M McBride
Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29119939/mannose-binding-lectin-protein-deficiency-among-patients-with-primary-immunodeficiency-disease-receiving-ivig-therapy
#16
Gholamreza Azizi, Fatemeh Kiaee, Naeimeh Tavakolinia, Hosein Rafiemanesh, Sara Mohammadikhajehdehi, Laleh Sharifi, Reza Yazdani, Hassan Abolhassani, Asghar Aghamohammadi
BACKGROUND: Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of the immune system are defective. Immunoglobulin replacement therapy is the mainstay of treatment for patients with impaired antibody production. However, recurrent infections would continue to occur in some patients due to the other high frequent concomitant defects such as mannose-binding lectin (MBL) deficiency. METHODS: A total of 51 PID patients participated in this cross-sectional study...
November 7, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29119074/case-report-on-a-defective-antibody-response-against-pneumococcal-serotype-9v-in-a-patient-with-a-single-episode-of-pneumonia
#17
Diana van Kessel, Thijs Hoffman, Heleen van Velzen-Blad, Bob Meek, Suzan van Mens, Jan Grutters, Ger Rijkers
Background: Patients with recurrent respiratory tract infections and an impaired response to pneumococcal polysaccharide vaccination are diagnosed with a specific antibody deficiency. In adult patients with pneumococcal pneumonia an impaired antibody response to the infecting pneumococcal serotype can sometimes be found. It is unknown whether these patients are unable to produce an adequate anti-polysaccharide antibody response to pneumococcal vaccination after recovery. Case presentation: The authors describe a case of invasive pneumonia caused by Streptococcus pneumoniae serotype 9V in a previously healthy 35-year-old female...
2017: Pneumonia
https://www.readbyqxmd.com/read/29118006/the-immunobiology-of-cd27-and-ox40-and-their-potential-as-targets-for-cancer-immunotherapy
#18
Sarah L Buchan, Anne Rogel, Aymen Al-Shamkhani
In recent years monoclonal antibodies (mAbs) able to reinvigorate anti-tumor T cell immunity have heralded a paradigm shift in cancer treatment. The most high profile of these mAbs block the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients across a range of tumor types. However, it is becoming increasingly clear that failure of some patients to respond to checkpoint inhibition is due to inadequate T-cell priming. For full T-cell activation two signals must be received and ligands providing the second of these signals, termed costimulation, are often lacking in tumors...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29115020/glycosylphosphatidylinositol-gpi-anchored-protein-deficiency-serves-as-a-reliable-reporter-of-pig-a-gene-mutation-support-from-an-in-vitro-assay-based-on-l5178y-tk-cells-and-the-cd90-2-antigen
#19
Jeffrey C Bemis, Svetlana L Avlasevich, Carson Labash, Page McKinzie, Javier Revollo, Vasily N Dobrovolsky, Stephen D Dertinger
Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk(+/-) . Cells were exposed to mutagenic and nonmutagenic compounds for 24 hr followed by washout and incubation for an additional 7 days. Following this mutant manifestation time, cells were labeled with fluorescent antibodies against CD90...
November 8, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#20
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
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