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https://www.readbyqxmd.com/read/28915952/iga-nephropathy-during-treatment-with-tnf-alpha-blockers-could-it-be-predicted
#1
Vito Di Lernia
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28912376/a-recombinant-human-adamts-13-first-in-human-study-evaluating-pharmacokinetics-safety-and-tolerability-in-cttp-patients
#2
Marie Scully, Paul Knöbl, Karim Kentouche, Lawrence Rice, Jerzy Windyga, Reinhard Schneppenheim, Johanna A Kremer Hovinga, Michiko Kajiwara, Yoshihiro Fujimura, Caterina Maggiore, Jennifer Doralt, Christopher Hibbard, Leah Martell, Bruce Ewenstein
Safety, tolerability and pharmacokinetics of recombinant ADAMTS-13 (rADAMTS-13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity < 6%) in a prospective phase 1, first-in-human, multicenter dose escalation study. BAX 930 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed. Following single dose administration of BAX 930 at 5, 20, or 40 U/kg body weight to adolescents and adults, there was approximate dose proportionality with respect to Cmax and AUC...
September 14, 2017: Blood
https://www.readbyqxmd.com/read/28912302/prevention-of-renal-apob-retention-is-protective-against-diabetic-nephropathy-role-of-tgf-%C3%AE-inhibition
#3
Patricia G Wilson, Joel C Thompson, Meghan H Yoder, Richard Charnigo, Lisa R Tannock
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy. We previously demonstrated that renal lipoproteins co-localize with biglycan, a renal proteoglycan. The purpose of this study was to determine if prevention of renal lipid (apoB) accumulation attenuates diabetic nephropathy. Biglycan deficient and biglycan wildtype Ldlr-/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated TGF-b, in some experiments mice were injected with either the TGF-b neutralizing antibody 1D11 or with 13C4, an irrelevant control antibody...
September 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28912267/antitumor-immunity-is-defective-in-t-cell-specific-microrna-155-deficient-mice-and-is-rescued-by-immune-checkpoint-blockade
#4
Thomas B Huffaker, Soh-Hyun Lee, William W Tang, Jared A Wallace, Margaret Alexander, Marah C Runtsch, Dane K Larsen, Jacob Thompson, Andrew G Ramstead, Warren P Voth, Ruozhen Hu, June L Round, Matthew A Williams, Ryan M O'Connell
MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911209/intracellular-activation-of-ovastacin-mediates-pre-fertilization-hardening-of-the-zona-pellucida
#5
Hagen Körschgen, Michael Kuske, Konstantin Karmilin, Irene Yiallouros, Melanie Balbach, Julia Floehr, Dagmar Wachten, Willi Jahnen-Dechent, Walter Stöcker
STUDY QUESTION: How and where is pro-ovastacin activated and how does active ovastacin regulate zona pellucida hardening (ZPH) and successful fertilization? STUDY FINDING: Ovastacin is partially active before exocytosis and pre-hardens the zona pellucida (ZP) before fertilization. WHAT IS KNOWN ALREADY: The metalloproteinase ovastacin is stored in cortical granules, it cleaves zona pellucida protein 2 (ZP2) upon fertilization and thereby destroys the ZP sperm ligand and triggers ZPH...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28905389/the-first-reported-case-of-concurrent-trimethoprim-sulfamethoxazole-induced-immune-hemolytic-anemia-and-thrombocytopenia
#6
Yevgeniy A Linnik, Edison W Tsui, Isabella W Martin, Zbigniew M Szczepiorkowski, Gregory A Denomme, Jerome L Gottschall, John M Hill, Nancy M Dunbar
BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes. CASE REPORT: A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine...
September 14, 2017: Transfusion
https://www.readbyqxmd.com/read/28905102/digestive-system-in-psoriasis-an-update
#7
REVIEW
Daniel Pietrzak, Aldona Pietrzak, Dorota Krasowska, Andrzej Borzęcki, Kinga Franciszkiewicz-Pietrzak, Beata Polkowska-Pruszyńska, Maja Baranowska, Kristian Reich
Psoriasis is a chronic inflammatory immune-mediated disorder associated and often coexisting with many other immune-related clinical conditions including those affecting the gastrointestinal tract. Data obtained from the reviewed literature suggest an association between psoriasis and pathologies of the oral cavity, both psoriasis-specific lesions, as well as non-specific, such as geographic tongue or fissured tongue. These findings show the importance of thorough examination of oral mucosa in psoriatic patients...
September 13, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28901173/cyclin-d2-is-a-critical-mediator-of-exercise-induced-cardiac-hypertrophy
#8
Stephen W Luckey, Chris D Haines, John P Konhilas, Elizabeth D Luczak, Antke Messmer-Kratzsch, Leslie A Leinwand
A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1(-/-)), and mice deficient in cyclin D2 (cyclin D2(-/-))...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#9
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900629/siae-rare-variants-in-juvenile-idiopathic-arthritis-and-primary-antibody-deficiencies
#10
Eirini Sevdali, Elena Tsitsami, Maria Tsinti, Evangelia Farmaki, Efimia Papadopoulou-Alataki, Anastasios E Germenis, Matthaios Speletas
Sialic acid acetylesterase (SIAE) deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA), yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA) and autoimmune oligo/polyarticular (aJIA), and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs), the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28898770/immunoglobulin-replacement-therapy-in-primary-and-secondary-antibody-deficiency-the-correct-clinical-approach
#11
REVIEW
Antonio Pecoraro, Ludovica Crescenzi, Francescopaolo Granata, Arturo Genovese, Giuseppe Spadaro
Immunoglobulin therapy is the administration of human polyvalent IgG and represents the most effective treatment to prevent recurrent infections in antibody deficiency patients. Primary antibody deficiency represents the main indication of immunoglobulin replacement therapy and includes a wide range of disorders characterized by impaired antibody production in response to pathogens and recurrent infections. However, not all primary antibody deficiency patients require immunoglobulin replacement. Indeed, immunoglobulin preparations are expensive and, once prescribed, usually result in lifelong therapy...
September 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28895870/protection-of-commercial-turkeys-following-inactivated-or-recombinant-h5-vaccine-application-against-the-2015u-s-h5n2-clade-2-3-4-4-highly-pathogenic-avian-influenza-virus
#12
Darrell R Kapczynski, Matthew J Sylte, Mary L Killian, Mia K Torchetti, Klaudia Chrzastek, David L Suarez
Between December 2014 and June 2015, North America experienced the largest recorded foreign animal disease outbreak with over 47 million poultry dead or euthanized from viral exposure to a clade 2.3.4.4 H5 highly pathogenic avian influenza (HPAI) epizootic. Soon after the epizootic began, the U.S. Department of Agriculture (USDA) began testing the efficacy of different vaccines as a possible future control strategy. The aim of these studies were to evaluate the efficacy three H5 vaccines to aid in control of HPAI in commercial turkeys...
September 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28893913/il17a-deficient-mice-are-highly-susceptible-to-toxoplasma-gondii-infection-due-to-excessively-induced-t-gondii-hsp70-and-ifn-%C3%AE-production
#13
Masataka Moroda, Masaya Takamoto, Yoichiro Iwakura, Jun Nakayama, Fumie Aosai
IL-17A is known to be involved in the host defense against pathogens and pathogenesis of autoimmune diseases. Previously, we showed that excessive IFN-γ plays an important role in the pathogenesis of lethal effect of Toxoplasma gondii (T. gondii) by inducing anaphylactic responses. In this report, we examine the effects of an IL-17A deficiency on murine host defense against oral T. gondii infection. IL-17A-deficient C57BL/6 (B6) mice exhibited higher mortality than wild type (WT) mice to T. gondii at the acute phase of infection...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#14
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
September 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28887841/evidence-for-a-contributory-role-of-a-xenogeneic-immune-response-in-experimental-epidermolysis-bullosa-acquisita
#15
Markus Niebuhr, Michael Kasperkiewicz, Sebastian Maass, Eva Hauenschild, Katja Bieber, Ralf J Ludwig, Jürgen Westermann, Kathrin Kalies
Autoimmune diseases affect a large fraction of the population in Western countries. To elucidate the underlying causes, autoantibody transfer-induced mouse models have been established that greatly contributed to the understanding of the pathophysiology of these diseases. However, the role of a potentially co-occurring murine xenogeneic immune response to commonly utilized rabbit anti-mouse IgG remains poorly understood. Using the established rabbit anti-mouse type VII collagen (COL7) IgG-induced mouse model of the mucocutaneous blistering disorder epidermolysis bullosa acquisita (EBA), we found in this study a profound T and B cell response along with an altered cytokine expression profile in draining lymph nodes of mice injected with the xenogeneic IgG...
September 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28887040/roles-of-antibodies-to-influenza-a-virus-hemagglutinin-neuraminidase-and-m2e-in-conferring-cross-protection
#16
Yu-Jin Kim, Eun-Ju Ko, Min-Chul Kim, Yu-Na Lee, Ki-Hye Kim, Yu-Jin Jung, Sang-Moo Kang
Although neuraminidase (NA) is the second major viral glycoprotein of influenza virus, its immune mechanism as a vaccine target has been less considered. Here we compared the properties of antibodies and the efficacy of cross protection by N1 and N2 NA proteins, inactivated split influenza vaccines (split), and tandem repeat extracellular domain M2 on virus-like particles (M2e5x VLP). Anti-NA immune sera could confer better cross-protection against multiple heterologous influenza viruses correlating with NA inhibition activity compared to split vaccine immune sera...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28886882/insights-into-defective-serological-memory-after-acute-lymphoblastic-leukaemia-treatment-the-role-of-the-plasma-cell-survival-niche-memory-b-cells-and-gut-microbiota-in-vaccine-responses
#17
REVIEW
Shanie Saghafian-Hedengren, Ismael Söderström, Eva Sverremark-Ekström, Anna Nilsson
Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of childhood cancer cases. As a result of effective treatments over the past decades, paediatric ALL mortality has been greatly reduced. Chemotherapy, however, has a range of harmful side effects including the loss of protective antibodies against vaccine-preventable diseases. Since ALL survivors have an increased risk of health problems including organ insufficiencies, acquired vaccine-preventable infections subsequent to clinical remission could become life threatening to these individuals...
August 26, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28882929/rhob-blockade-selectively-inhibits-autoantibody-production-in-autoimmune-models-of-rheumatoid-arthritis-and-lupus
#18
Laura Mandik-Nayak, James B DuHadaway, Jennifer Mulgrew, Elizabeth Pigott, Kaylend Manley, Summer Sedano, George C Prendergast, Lisa D Laury-Kleintop
During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells favoring the production of pathogenic versus non-pathogenic autoantibodies. However, there is limited knowledge concerning how this pivotal step occurs. Here we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical model of inflammatory arthritis...
September 7, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28881511/-role-of-igg-antibody-to-galactose-deficient-iga1-in-children-with-iga-nephropathy
#19
N Zhou, H Zhang, X R Liu, Q Sun, Q Meng, Z Chen, Y Shen
Objective: In order to learn the serum level of galactose-deficient IgA1 (GdIgA1), IgG antibody to galactose-deficient IgA1(GdIgA1-IgG) and the clinical role of them in IgA nephropathy(IgAN) children. Method: We compared blood levels of GdIgA1, GdIgA1-IgG in 33 children with IgAN, 38 children with other renal disease (including focal segmental glomerular nephritis, minimal change disease, Alport syndrome and thin basement membrane nephropathy) as disease controls, 35 healthy children as normal controls with enzyme-linked immunosorbent assay(ELISA)...
September 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28880403/natural-igm-initiates-an-inflammatory-response-important-for-both-hepatic-ischemia-reperfusion-injury-and-regeneration
#20
Keely Marshall, Junfei Jin, Carl Atkinson, Ali Alawieh, Fei Qiao, Biao Lei, Kenneth D Chavin, Songqing He, Stephen Tomlinson
RATIONALE: Complement plays a role in both hepatic ischemia reperfusion (IR) injury (IRI) and liver regeneration, but it is not clear how complement is activated in either process. We investigated the role of self-reactive IgM antibodies in activating complement after hepatic IR and liver resection. MAIN RESULTS: Natural IgM antibodies that recognize danger associated molecular patterns (neoepitopes) activate complement following both hepatic IR and liver resection...
September 7, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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