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antibody deficiency

Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
Youping Wu, Chun-Shiang Chung, Yaping Chen, Sean Farrell Monaghan, Sima Patel, Xin Huang, Daithi Seamus Heffernan, Alfred Ayala
Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction...
October 25, 2016: Molecular Medicine
Petra D Cravens, Rehana Z Hussain, William A Miller-Little, Li-Hong Ben, Benjamin M Segal, Emily Herndon, Olaf Stüve
BACKGROUND: Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS...
2016: PloS One
Mehdi Hassanpour, Omid Cheraghi, Vahid Siavashi, Reza Rahbarghazi, Mohammad Nouri
Introduction: A large number of cardiovascular disorders and abnormalities, notably accelerated vascular deficiencies could be related to aging changes and increased length of life. During the past decades, the discovery of different stem cells facilitates ongoing attempts for attenuating many disorders, especially in vascular beds. Endothelial progenitor cells (EPCs) are a subtype of stem cells that have potent capacity to differentiate into mature endothelial cells (ECs). However, some documented studies reported an age-related decline in proliferation and function of many stem cells...
2016: Journal of Cardiovascular and Thoracic Research
Soyoung Lee, Han Wool Kim, Kyung-Hyo Kim
BACKGROUND: Intravenous immunoglobulin G (IVIG) replacement therapy is used to prevent invasive infections in patients with primary antibody deficiency (PAD). However, few studies have functionally evaluated specific antibodies against encapsulated bacteria that cause invasive infection in patients with PAD. In this study, functional antibodies against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococci), and Neisseria meningitidis (meningococci) in IVIG therapy were evaluated...
October 23, 2016: Transfusion
Denise Mathes, Johannes Weirather, Peter Nordbeck, Anahi-Paula Arias-Loza, Matthias Burkard, Christina Pachel, Thomas Kerkau, Niklas Beyersdorf, Stefan Frantz, Ulrich Hofmann
OBJECTIVE: The present study analyzed the effect of CD4(+) Forkhead box protein 3 negative (Foxp3(-)) T-cells and Foxp3(+) CD4(+) T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. APPROACH AND RESULTS: We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4(+) T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34...
October 19, 2016: Journal of Molecular and Cellular Cardiology
Marrit N Habets, Saskia van Selm, Fred J van Opzeeland, Elles Simonetti, Peter W M Hermans, Marien I de Jonge, Dimitri A Diavatopoulos
Widespread vaccination against Streptococcus pneumoniae (the pneumococcus) has significantly reduced pneumococcal disease caused by vaccine serotypes. Despite vaccination, overall pneumococcal colonization rates in children have not reduced and otitis media (OM) by non-vaccine serotypes remains one of the most common childhood infections. Pneumococcal surface protein A (PspA) has been shown to be a promising protein antigen to induce broad protection against pneumococcal colonization. However, its ability to protect against OM remains unclear...
October 19, 2016: Vaccine
Louise Hetherington, Elena Schneider, Caroline Scott, David DeKretser, Charles H Muller, Hubert Hondermarck, Tony Velkov, Mark A Baker
Globally, approximately 1 in 15 men of reproductive age are infertile, yet the precise mechanisms underlying their gamete failure are unknown. Although a semen-analysis is performed to determine fertilizing potential, the diagnostic suitability of this analysis has been questioned in several reports, as many men, classified as "infertile" according to their semen analysis, subsequently turn out to be fertile. Herein, we have used a quantitative (phospho)-proteomic analysis, using enrichment on titanium dioxide followed by ion-trap mass spectrometry (LC-MS/MS), to compare the semen of infertile versus fertile males...
October 21, 2016: Molecular & Cellular Proteomics: MCP
Pang Yao, Liang Sun, Ling Lu, Hong Ding, Xiafei Chen, Lixin Tang, Xinming Xu, Gang Liu, Yao Hu, Yiwei Ma, Feijie Wang, Qianlu Jin, He Zheng, Huiyong Yin, Rong Zeng, Yan Chen, Frank B Hu, Huaixing Li, Xu Lin
CONTEXT: Little is known how genetic and non-genetic factors modify responses of vitamin D supplementation in nonwhite populations. OBJECTIVE: To investigate factors modifying 25-hydroxyvitamin D (25[OH]D) and bioavailable 25(OH)D (25[OH]DBio) responses after vitamin D3 supplementation. Design, Setting, Participants, and Intervention: In this randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency (25[OH]D<50 nmol/L) received 2000 IU/d vitamin D3 or placebo for 20 weeks...
October 21, 2016: Journal of Clinical Endocrinology and Metabolism
Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
S T Oestergaard, T Stojkovic, J R Dahlqvist, C Bouchet-Seraphin, J Nectoux, F Leturcq, M Cossée, G Solé, C Thomsen, T O Krag, J Vissing
OBJECTIVE: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. METHODS: Six new patients with genetically verified mutations in GMPPB were studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting...
December 2016: Neurology. Genetics
Carol H Miao
Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect...
2016: Thrombosis Journal
Reza Yazdani, Gholamreza Azizi, Hassan Abolhassani, Asghar Aghamohammadi
Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients suffer from different clinical complications such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Pathogenesis of SIgAD is still unknown, however, a defective terminal differentiation of B-cells and defect in switching to IgA-producing plasma cells are presumed to be responsible. Furthermore, some cytogenic defects and monogenic mutations are associated with SIgAD...
October 20, 2016: Scandinavian Journal of Immunology
Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B cell-deficient μMT mice or CD20 antibody-mediated B cell depleted mice...
October 20, 2016: Journal of Pathology
Sarah C Bath, Victor J M Pop, Victoria L Furmidge-Owen, Maarten Broeren, Margaret P Rayman
Background Though iodine deficiency in pregnancy is a matter of public-health concern, a functional measure of iodine status is lacking. The thyroid-specific protein, thyroglobulin (Tg), which reflects thyroid size, has shown promise as a functional measure in studies of children and adults, but data in pregnancy are sparse. In a cohort of mildly-to-moderately iodine-deficient pregnant women, we aimed to explore whether serum Tg is a sensitive functional biomarker of iodine status and to examine longitudinal change in Tg with gestational age...
October 20, 2016: Thyroid: Official Journal of the American Thyroid Association
Leon E Hugo, Natalie A Prow, Bing Tang, Greg Devine, Andreas Suhrbier
BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with epidemics of acute and chronic arthritic disease in humans. Aedes albopictus has emerged as an important new natural vector for CHIKV transmission; however, mouse models for studying transmission have not been developed. METHODS: Aedes albopictus mosquitoes were infected with CHIKV via membrane feeding and by using infected adult wild-type C57BL/6 mice. Paraffin sections of infected mosquitoes were analysed by immunofluorescent antibody staining using an anti-CHIKV antibody...
October 19, 2016: Parasites & Vectors
Derek D Jones, Brian T Gaudette, Joel R Wilmore, Irene Chernova, Alexandra Bortnick, Brendan M Weiss, David Allman
Little is known about the role of mTOR signaling in plasma cell differentiation and function. Furthermore, for reasons not understood, mTOR inhibition reverses antibody-associated disease in a murine model of systemic lupus erythematosus. Here, we have demonstrated that induced B lineage-specific deletion of the gene encoding RAPTOR, an essential signaling adaptor for rapamycin-sensitive mTOR complex 1 (mTORC1), abrogated the generation of antibody-secreting plasma cells in mice. Acute treatment with rapamycin recapitulated the effects of RAPTOR deficiency, and both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating preexisting germinal centers...
October 17, 2016: Journal of Clinical Investigation
Afshin Shirkani, Mohammad Shahrooei, Gholamreza Azizi, Hassan Rokni-Zadeh, Hassan Abolhassani, Shokrollah Farrokhi, Glynis Frans, Xavier Bossuyt, Asghar Aghamohammadi
ZAP-70 deficiency is a rare autosomal recessive form of combined immunodeficiency (CID) characterized by selective absence of circulating CD8 T cells with low, normal, or increased CD4 T cells in peripheral blood. Up to now, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID. We present a 3-year-old boy with a history of recurrent bacterial infections and autoimmunity. Initial laboratory findings showed a normal total lymphocyte count, but low levels of CD8 and CD4 T cells and an abnormal lymphocyte proliferation response...
October 19, 2016: Immunological Investigations
Bagirath Gangadharan, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Maud Teyssandier, Srinivas V Kaveri, Sébastien Lacroix-Desmazes
The development of inhibitory antibodies to therapeutic FVIII is the major complication of replacement therapy in patients with hemophilia A. The first step in the initiation of the anti-FVIII immune response is FVIII interaction with receptor(s) on antigen-presenting cells followed by endocytosis and presentation to naive CD4+ T cells. Recent studies indicate a role for the C1 domain in FVIII uptake. We investigated whether charged residues in the C2 domain participate in immunogenic FVIII uptake. Co-incubation of FVIII with BO2C11, a monoclonal C2-specific IgG, reduced FVIII endocytosis by dendritic cells and presentation to CD4+ T cells, and diminished FVIII immunogenicity in FVIII-deficient mice...
October 6, 2016: Haematologica
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
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