Human Immunology News Volume 1.01 | Mar 19 2013

PUBLICATIONS (Ranked by impact factor of the journal)

B Cells Promote Inflammation in Obesity and Type 2 Diabetes through Regulation of T-Cell Function and an Inflammatory Cytokine Profile
Investigators demonstrated that B cells from type 2 diabetes (T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. [Proc Natl Acad Sci USA]
Abstract | Press Release

Long-Term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-Cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer
Researchers performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed. [Clin Cancer Res] Abstract

PhIP-Seq Characterization of Autoantibodies from Patients with Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis
Investigators present data from a large-scale screen of 298 independent antibody repertoires, including those from 73 healthy sera, using phage immunoprecipitation sequencing. The resulting database of peptide-antibody interactions characterizes each individual’s unique autoantibody fingerprint, and includes specificities found to occur frequently in the general population as well as those associated with disease. [J Autoimmunity] Abstract

Regulation of IL-17A Production Is Distinct from IL-17F in a Primary Human Cell Co-Culture Model of T Cell-Mediated B Cell Activation
Scientists aimed to characterize the regulation of IL-17A and IL-17F in a model of T cell-dependent B cell activation. Stimulation of primary human B cell and peripheral blood mononuclear cell co-cultures with α-IgM and a non-mitogenic concentration of superantigens for three days promoted a T helper 17 (Th17) cell response as evidenced by increased expression of Th17-related gene transcripts, including Il17f, Il21, Il22, and Il23r, in CD4 T cells, as well as the secretion of IL-17A and IL-17F protein. [PLoS One] Full Article

Activation of the Type I Interferon Pathway Is Enhanced in Response to Human Neuronal Differentiation
Researchers used an established neuronal cell line model and an embryonic stem cell-based system to examine human neuronal innate immunity and responses to neurotropic alphavirus infection in cultured cells. They demonstrated that neuronal differentiation is associated with increased expression of crucial type I interferon signaling pathway components, including interferon regulatory factor-9 and an interferon receptor heterodimer subunit, which results in enhanced interferon stimulation and subsequent heightened antiviral activity and cytoprotective responses against neurotropic alphaviruses such as western equine encephalitis virus. [PLoS One] Full Article

Tim-3 Alters the Balance of IL-12/IL-23 and Drives T_H17 Cells: Role in Hepatitis B Vaccine Failure during Hepatitis C Infection
The authors investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in Hepatitis B virus (HBV) vaccine responses during hepatitis C virus (HCV) infection. They found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production, which in turn T_H17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects. [Vaccine] Abstract

Characterization of Th1- and Th2-Associated Chemokine Receptor Expression in Spleens of Patients with Immune Thrombocytopenia
In view of the numerous clinical observations and laboratory studies that suggest a critical role for the spleen in immune thrombocytopenia (ITP) pathophysiology, scientists aimed to characterize Th1-associated chemokine receptors CXCR3 and CCR5 and Th2-associated chemokine receptor CCR3 in spleens of ITP patients and assess the significance of their differential expression in the clinical setting. [J Clin Immunol] Abstract

Progress Towards Inducing Immunologic Tolerance to Factor VIII
This review highlights recent progress towards the related goals of lowering the incidence of anti-therapeutic factor VIII (FVIII) immune responses and promoting durable, functional immune tolerance to FVIII in hemophilia A patients with an existing inhibitor. [Blood] Abstract

Immune Cell Dysfunction and Inflammation in End-Stage Renal Disease
Uraemia causes inflammation and reduces immune system function as evidenced by an increased risk of viral-associated cancers, increased susceptibility to infections and decreased vaccination responses in patients with end-stage renal disease (ESRD). Similar to healthy elderly individuals, patients with ESRD have increased numbers of specific proinflammatory subsets of T cells and monocytes, suggesting the presence of premature immunological ageing in these patients. [Nat Rev Nephrol] Abstract

New Targets for the Immunotherapy of Colon Cancer-Does Reactive Disease Hold the Answer?
The authors review the state-of-the-art for colorectal cancer (CRC) with respect to the expression of cancer-testis antigens (CTAs) and their identification, evaluation and correlation with disease progression, treatment response and survival. They also discuss the relationship between CTA expression and regulatory T-cell activity to tumorigenesis and tumor immune evasion in CRC and how this could account for the clinical presentation of CRC. [Cancer Gene Ther] Abstract

£1.7 Million Boost for Research Into Inflammatory and Autoimmune Diseases
Research at the University of Dundee targeting the cause of inflammatory and autoimmune diseases, which affect millions of people has been boosted by a grant of almost £1.7million from the Wellcome Trust. The work is aimed at unravelling the workings of a genetic pathway – known as the MyD88 signaling pathway – which operates as part of our innate immune system. [University of Dundee] Press Release

Virobay and LEO Pharma Initiate a Phase I Trial of VBY-891, a Compound Intended for Oral Treatment of Psoriasis
Virobay, Inc. and LEO Pharma A/S announced that their collaboration on the development of an oral treatment for psoriasis has reached an important milestone as Virobay has now initiated a Phase I clinical trial of VBY-891 – a selective cathepsin S inhibitor. The first Phase I trial of VBY-891 is a double-blind, randomized, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of VBY-891 in healthy adults. [Virobay, Inc.] Press Release

ImmunoCellular Therapeutics Announces Issuance of Key Patent for ICT-121 Cancer Vaccine
ImmunoCellular Therapeutics, Ltd. announced that the US Patent and Trademark Office has issued a key patent application covering ICT-121, an immunotherapeutic vaccine targeting CD133, an important cancer stem cell marker that is commonly overexpressed on a broad range of solid tumors. The patent includes claims covering composition of matter as well as methods of use. [ImmunoCellular Therapeutics, Ltd.]
Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Keystone Symposia on Molecular and Cellular Biology: Immune Activation in HIV Infection- Basic Mechanisms and Clinical Implications
April 3-8, 2013
Breckenridge, United States

NEW Keystone Symposia on Molecular and Cellular Biology: Immunopathology of Type 1 Diabetes
April 4-9, 2013
Whistler, Canada

NEW Keystone Symposia on Molecular and Cellular Biology: Advances in the Knowledge and Treatment of Autoimmunity
April 4-9, 2013
Whistler, Canada

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Postdoctoral Position – Type 1 Diabetes and Systemic Lupus Erythematosus (University of Florida)

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