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Sven Jarius, Marius Ringelstein, Jürgen Haas, Irina I Serysheva, Lars Komorowski, Kai Fechner, Klaus-Peter Wandinger, Philipp Albrecht, Harald Hefter, Andreas Moser, Eva Neuen-Jacob, Hans-Peter Hartung, Brigitte Wildemann, Orhan Aktas
BACKGROUND: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to ITPR1 may be broader than initially thought...
October 24, 2016: Journal of Neuroinflammation
Ni Lin, Tiantian Liu, Lin Lin, Sheng Lin, Qingce Zang, Jiuming He, Zeper Abliz, Chao Li, Aiping Wang, Hongtao Jin
The standard of 5-Hydroxymethylfurfural (5-HMF) existed in dextrose injection as an inevitable by-product during high-temperature setrilization has been included in pharmacopoeias considering its hazardous effects on human health. We found that the concentrations of 5-HMF in some traditional Chinese medicine injections (TCMIs) far exceeded its limit in dextrose injection. Besides, we detected 5, 5'-Oxydimethylenebis (2-furfural) (OMBF) in those TCMIs containing high concentrations of 5-HMF. We investigated the in vivo immunomodulatory effects of 5-HMF and OMBF at three dose levels using the reporter antigen popliteal lymph node assay (RA-PLNA), which allows the straightforward examination and mechanistic study of immunotoxicity of low molecular weight compounds...
October 17, 2016: Regulatory Toxicology and Pharmacology: RTP
Patricia Rubio Reyes, Natalie A Parlane, D Neil Wedlock, Bernd H A Rehm
Traditional approaches to vaccine development have failed to identify better vaccines to replace or supplement BCG for the control of tuberculosis (TB). Subunit vaccines offer a safer and more reproducible alternative for the prevention of diseases. In this study, the immunogenicity of bacterially derived polyester beads displaying three different Rv antigens of Mycobacterium tuberculosis was evaluated. Polyester beads displaying the antigens Rv1626, Rv2032, Rv1789, respectively, were produced in an endotoxin-free Escherichia coli strain...
October 13, 2016: International Journal of Medical Microbiology: IJMM
Luise Appeltshauser, Andreas Weishaupt, Claudia Sommer, Kathrin Doppler
Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3...
October 13, 2016: Experimental Neurology
R L Ferris, J L Geiger, S Trivedi, N C Schmitt, D E Heron, J T Johnson, S Kim, U Duvvuri, D A Clump, J E Bauman, J P Ohr, W E Gooding, A Argiris
BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes)...
October 11, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Andreas J Hülsmeier, Micha Tobler, Patricie Burda, Thierry Hennet
Glycosylation is an integral part in health and disease, as emphasized by the growing number of identified glycosylation defects. In humans, proteins are modified with a diverse range of glycoforms synthesized in complex biosynthetic pathways. Glycosylation disorders have been described in congenital disorders of glycosylation (CDG) as well as in acquired disease conditions such and non-alcoholic fatty liver disease (NAFLD). A hallmark in a subset of CDG cases is the reduced glycosylation site occupancy of asparagine-linked glycans...
October 11, 2016: Scientific Reports
M Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Psoriasis is a complex disease in which the alteration of the IL-23/Th17 axis appears to be crucial for its pathogenic mechanisms, and anti-IL17 agents are rapidly becoming important therapeutic tools. 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. Areas covered: A PubMed search was performed for relevant literature...
October 10, 2016: Expert Review of Clinical Immunology
Matthew Peach, Ren Xu, Dan Fitzpatrick, Lisa Hamilton, Ransi Somaratne, Rob Scott, Scott M Wasserman, C Stephen Djedjos
The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. PCSK9 inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-C, but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial...
October 5, 2016: Journal of Lipid Research
Raquel Moya, Jerónimo Carnés, Nuria Sinovas, Laura Ramió, Pilar Brazis, Anna Puigdemont
BACKGROUND: Canine atopic dermatitis is a pruritic allergic skin disease. House dust mites have been identified as the main non-seasonal responsible agent. Unlike in human allergic patients, groups 1 and 2 antigens have been described as minor allergens in dogs, while groups 15 and 18 are considered the major allergens. Despite these differences, allergic dogs have traditionally been treated using extracts intended for human immunotherapy. OBJECTIVES: To investigate the immunological characteristics and the allergen reactivity of dogs with atopic dermatitis using a Dermatophagoides farinae commercial extract...
November 1, 2016: Veterinary Immunology and Immunopathology
Daniel Sánchez, Pavel Gregor, Karol Čurila, Iva Hoffmanová, Věra Hábová, Ludmila Tučková, Helena Tlaskalová-Hogenová
Distinct cellular level of the Ca(2+)-binding chaperone calreticulin (CRT) is essential for correct embryonal cardiac development and postnatal function. However, CRT is also a potential autoantigen eliciting formation of antibodies (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac injury, while overexpression of CRT in cardiomyocytes induces dilated cardiomyopathy (DCM) in animals. Hence, we analysed levels of anti-CRT Ab and calreticulin in the sera of patients with idiopatic DCM and hypertrophic cardiomyopathy (HCM)...
September 30, 2016: Autoimmunity
Y-H Fan, Y-L Lin, Y-C Hwang, H-C Yang, H-C Chiu, S-H Chiou, M-H Jong, K-C Chow, C-C Lin
The effect of co-administration of interferon (IFN)-γ in pigs undergoing vaccination with an attenuated strain (LPC) of classical swine fever virus (CSFV) was investigated. Unvaccinated pigs demonstrated pyrexia and died 7-9 days after challenge with virulent CSFV. Pigs receiving the attenuated vaccine remained healthy after virus challenge, except for mild, transient pyrexia, whereas pigs receiving IFN-γ simultaneously with the vaccine demonstrated normal body temperatures after virus challenge. Examination by nested RT-PCR revealed greater viral load in the spleens of the pigs vaccinated with the attenuated CSFV, compared with those that had additionally received IFN-γ...
October 2016: Veterinary Journal
Jeffrey T Guptill, Vern C Juel, Janice M Massey, Amanda C Anderson, Manisha Chopra, John S Yi, Ehsanollah Esfandiari, Tim Buchanan, Bryan Smith, Paul Atherfold, Emma Jones, James F Howard
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation...
August 11, 2016: Autoimmunity
John P Gibbs, J Greg Slatter, Ogo Egbuna, Michelle Geller, Lisa Hamilton, Clapton S Dias, Ren Y Xu, Jessica Johnson, Scott M Wasserman, Maurice G Emery
Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL-C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, and safety in individuals with and without hepatic impairment. Open-label, parallel-group study evaluating the pharmacokinetics of evolocumab in hepatic-impaired (Child-Pugh Class A or B) or healthy adults...
September 26, 2016: Journal of Clinical Pharmacology
Jamshaid Iqbal, Jumanah Al-Rashed, Elijah O Kehinde
BACKGROUND: Despite a worldwide common and progressive nature of benign prostate hyperplasia (BPH) in older men, no association has been observed between a causative pathogen and other etiology so far. METHODS: In this study, we investigated a causative association of Trichomonas vaginalis, a flagellate protozoan parasite, in 171 BPH cases presenting without symptoms of prostatitis at a surgical outpatient clinic in Kuwait. We detected T. vaginalis DNA by polymerase chain reaction (PCR) and T...
2016: BMC Infectious Diseases
R Cianci, S Lolli, D Pagliari, G Gambassi, S Frosali, R Marmo, G Melioli, A Orlando, E E Newton, E Serone, R Landolfi, F Pandolfi, D Frezza
OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections...
September 2016: European Review for Medical and Pharmacological Sciences
Heather L Howie, Meghan Delaney, Xiaohong Wang, Lay See Er, Gestur Vidarsson, Tamara C Stegmann, Linda Kapp, Jenna N Lebedev, Yanyun Wu, James P AuBuchon, James C Zimring
BACKGROUND: Human immunoglobulin G (IgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4), and it is also now appreciated that there are genetic variations within IgG subtypes (called isoallotypes). Twenty-nine different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1, IgG2, IgG3, and IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized. STUDY DESIGN AND METHODS: A novel monoclonal anti-K antibody (PugetSound Monoclonal Antibody 1 [PUMA1]) was isolated and sequenced, and a panel of PUMA1 variants was expressed, consisting of the 29 known IgG isoallotypes...
September 16, 2016: Transfusion
Rupert Weaver, Linda Reiling, Gaoqian Feng, Damien R Drew, Ivo Mueller, Peter M Siba, Takafumi Tsuboi, Jack S Richards, Freya J I Fowkes, James G Beeson
Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children...
September 8, 2016: Scientific Reports
Mark Christian Tjiam, Lucy Sariputra, Jesse D Armitage, James P A Taylor, Anthony D Kelleher, Dino B A Tan, Silvia Lee, Sonia Fernandez, Martyn A French
OBJECTIVES: We have previously demonstrated that HIV-1 p24-specific plasmacytoid dendritic cell (pDC)-reactive opsonophagocytic antibody (PROAb) responses associate with control of chronic HIV infection. Here, we examined whether HIV-1 p24-specific PROAbs associate with control of early HIV infection and their relationship with HIV-1 p24-specific IgG subclasses. METHODS: Plasma collected at 8 and 52 weeks following primary HIV-1 infection was obtained from antiretroviral therapy-naive patients who were classified as 'good' (plasma HIV-1 RNA < 5,000 copies/mL; n = 17) or 'poor' (HIV-1 RNA >50,000 copies/mL; n = 15) controllers at week 52...
September 6, 2016: AIDS
Yoshitaka Nishijima, Saya Taniguchi, Shuntaro Ikeda, Kenichi Yoshitani, Takashi Hamano, Hiroshi Tani, Masahiko Fujita, Kenji Murakami, Keisuke Kogusa, Kenji Sato, Miki Sugimoto, Shinichi Kume
Data from 18 β-carotene-deficient Japanese Black cows were collected to clarify the effects of feeding β-carotene-enriched dry carrots on β-carotene status and colostral immunoglobulin (Ig) in cows. Cows were assigned to control or carrot groups from 3 weeks before the expected calving date to parturition, and supplemental β-carotene from dry carrots was 138 mg/day in the carrot group. Plasma β-carotene concentrations in the control and carrot groups at parturition were 95 and 120 μg/dL, and feeding dry carrots slightly improved plasma β-carotene at parturition...
September 4, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
Michael Mattie, Arthur Raitano, Kendall Morrison, Karen Morrison, Zili An, Linette Capo, Alla Verlinsky, Monica Leavitt, Jimmy Ou, Rossana Nadell, Hector Avina, Claudia Guevara, Faisal Malik, Ruth Moser, Steven Duniho, Jeffrey Coleman, Ying Li, Daniel S Pereira, Fernando Donate, Ingrid B J Joseph, Pia M Challita-Eid, Dennis Benjamin, David R Stover
Here we report the development of an antibody-drug conjugate, ASG-5ME, which targets the solute carrier receptor SLC44A4. SLC44A4 is a member of a family of putative choline transporters which we show to be markedly upregulated in a variety of epithelial tumors, most notably prostate and pancreatic cancer. SLC44A4 is normally expressed on the apical surface of secretory epithelial cells but in cancer we show expression is not restricted to the luminal surface in advanced and undifferentiated tumors. ASG-5ME consists of a human IgG2 anti-SLC44A4 antibody conjugated through a cleavable linker to the microtubule-disrupting agent, monomethylauristatin E...
August 22, 2016: Molecular Cancer Therapeutics
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