Volume 1.04 | Apr 9

Human Immunology News 1.04 April 9, 2013
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Interleukin-1 Antagonism in Type 1 Diabetes of Recent Onset: Two Multicenter, Randomized, Double-Blind, Placebo-Controlled Trials
Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomized, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. Researchers aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved β-cell function in recent-onset type 1 diabetes. [Lancet] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

Increased Th17 Response to Pathogen Stimulation in Patients with Primary Sclerosing Cholangitis
In primary sclerosing cholangitis (PSC), bile fluid is frequently colonized with pathogens and its strong association with inflammatory bowel disease suggests the contribution of pathogen responses to disease pathogenesis. IL17A, the signature cytokine of Th17 cells, was recently described to promote inflammation and fibrosis within the liver. Researchers therefore investigated the Th17 immune response to pathogens in patients with PSC. [Hepatology] Abstract

Neutrophils Promote 6-Sulfo LacNAc+ Dendritic Cell (slanDC) Survival
The data presented not only expand the knowledge on the interactions between human neutrophils and slanDCs but also prove that neutrophil-mediated promotion of slanDC survival and potentiation of slanDC-derived IL-12p70 occur via different mechanisms. [J Leukoc Biol] Abstract

Dysferlin Regulates Cell Adhesion in Human Monocytes
Scientists showed that dysferlin expression is increased with differentiation in human monocytes and the THP1 monocyte cell model. Freshly isolated monocytes of dysferlinopathy patients showed deregulated expression of fibronectin and fibronectin binding integrins, which was recapitulated by transient knockdown of dysferlin in THP1 cells. [J Biol Chem] Abstract | Full Article

The TNF-Family Cytokine TL1A Inhibits Proliferation of Human Activated B Cells
Researchers describe for the first time that B cells from human blood express significant amounts of DR3 in response to B cell receptor polyclonal stimulation. The relevance of these results was confirmed by immunofluorescence analysis in tonsil and spleen tissue specimens, which showed the in situ expression of DR3 in antigen-stimulated B cells in vivo. [PLoS One] Full Article

Immunogenicity of Mycobacterial Vesicles in Humans: Identification of a New Tuberculosis Antibody Biomarker
The authors evaluated the human immune responses to BCG and Mycobacterium tuberculosis membrane vesicles (MVs) to characterize the antibody responses and identify potentially novel tuberculosis (TB) biomarkers. Serological responses to MVs were evaluated by ELISAs and immunoblots with sera from 16 sputum smear-positive, 12 smear-negative HIV uninfected pulmonary TB patients and 16 BCG vaccinated Tuberculin skin-test positive controls with and without latent tuberculosis infection. [Tuberculosis] Abstract

Sources of Heterogeneity in Human Monocyte Subsets
Using PBMCs from populations with differing ethnicities and histories of parasite exposure, researchers characterized monocyte phenotype based on intensity of CD14 and CD16 expression. Using the surface markers HLA-DR, CCR2 and CX3CR1, they compared monocyte phenotype between populations and further assessed changes in monocytes with freezing and thawing of PBMCs. [Immunol Lett] Abstract

Seasonal Influence on Mitogen and Cyclosporin Responses of Peripheral Blood Lymphocytes
Researchers examined the effects of season on the ex vivo mitogen-induced activation of lymphocytes from peripheral blood of healthy humans living in a temperate climate, as well as the ex vivo lymphocyte activation of rabbits living under constant laboratory conditions. The possible impact of season on the action of the immunosuppressant drug cyclosporin A on lymphocyte activation was investigated in both species. [Int Immunopharmacol] Abstract

Changes in Maternal Secretory Immunoglobulin A Levels in Human Milk during 12 Weeks After Parturition
Immune factors in human milk change in concentration after delivery. However, this concentration change during the early postpartum period has not yet been investigated in detail. The authors measured Secretory IgA levels in the human milk of 91 postpartum mothers by using an enzyme immunoassay, in postpartum day 3, and weeks 1, 2, 3, 4, 8, and 12. [Am J Hum Biol] Abstract

C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity
Testing >20 human lymphoma and leukemia B cell lines, researchers found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. [Cell Rep] Abstract | Graphical Abstract | Press Release

Host Responses in Human Skin After Conventional Intradermal Injection or Microneedle Administration of Virus-Like-Particle Influenza Vaccine
As skin immunization studies are generally restricted to animal models, where skin architecture and immunity is greatly different to human, surprisingly little is known about the local human response to intradermal vaccines. Researchers use surgically excised human skin to explore for the first time the complex molecular and cellular host responses to a candidate influenza vaccine comprising nanoparticulate virus-like-particles, administered via conventional hypodermic injection or reduced scale microneedles. [Adv Healthc Mater] Abstract

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Ectopic Germinal Centers, BAFF and Anti-B-Cell Therapy in Myasthenia Gravis
This article reviews the role of B cells in myasthenia gravis (MG). The authors first describe what is known about B cells in this disease and examine the involvement of the B cells in the thymus of MG patients. They detail the role of factors associated with B-cell function such as BAFF. Finally, they discuss the effects of therapy targeting B cells. [Autoimmun Rev] Abstract

Costimulatory Molecules on Immunogenic versus Tolerogenic Human Dendritic Cells
This review gives an overview of functional different human dendritic cell (DC) subsets with unique profiles of costimulatory molecules and outlines how different costimulatory pathways together with the immunosuppressive cytokine IL-10 bias immunogenic versus tolerogenic DC functions. Furthermore, the authors exemplarily describe protocols for the generation of two well-defined monocyte-derived DC subsets for their clinical use, immunogenic versus tolerogenic. [Front Immunol] Abstract

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Immunotherapy Showed Promising Antileukemia Activity in Pediatric Patients
Researchers using patients’ own immune cells in an immunotherapy approach called “anti-CD19 chimeric antigen receptor T-cell therapy,” achieved responses in children whose acute lymphocytic leukemia had returned after a bone marrow transplant, according to preliminary results. [Press release from the American Association for Cancer Research (AACR) discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

Two-Step Ovarian Cancer Immunotherapy Made from Patients’ Own Tumor Benefits Three Quarters of Trial Patients
As many as three quarters of advanced ovarian cancer patients appeared to respond to a new two-step immunotherapy approach, including one patient who achieved complete remission. The immunotherapy has two steps – a personalized dendritic cell vaccination and adoptive T-cell therapy. The team reports that in the study of 31 patients, vaccination therapy alone showed about a 61 percent clinical benefit, and the combination of both therapies showed about a 75 percent benefit. [Press release from the Perelman School of Medicine at the University of Pennsylvania discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

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ACGT Provides Seed Money for T-Cell Immunotherapy Cell and Gene Therapy Research; Successful Clinical Trials for Treatment of Lymphoblastic Leukemia Result in Remissions
ACGT announced that seed money provided for innovative T-Cell immunotherapy cell and gene therapy research has led to two successful Clinical Trials for treatment of Acute Lymphoblastic Leukemia resulting in remissions in both children and adults who had no other hope of recovery. [PR Web] Press Release

Researchers to Develop Next Generation Immunotherapy for Children with Deadly Solid Tumors
Researchers at the Children’s Hospital of Philadelphia, the University of Pennsylvania, and the Primary Children’s Medical Center of Salt Lake City received a $550,000 collaborative grant to test next generation T-cell immunotherapy strategies in children with neuroblastoma. The awardees were selected within a rigorous peer-review process through a new initiative called ACT FAST (Adoptive Cell Therapy For Adolescent/pediatric Solid Tumor), which is spearheaded by Solving Kids’ Cancer. [Solving Kids’ Cancer] Press Release

Genalyte Streamlines Immunogenicity Testing with Launch of MT-ADATM Assay for Real-Time Detection of Anti-Drug Antibodies
Genalyte, Inc. announced the launch of its MT-ADATM anti-drug antibody (ADA) immunogenicity assay designed to run on the MaverickTM Detection System. This test combines screening for the presence of ADAs and the characterization of each detected ADA with a full isotype profile. [Genalyte, Inc.]
Press Release


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NEW The Jackson Laboratory: Modeling Human Malignancy with Patient-Derived Xenograft Cancer Models
April 18, 1:00PM (ET in US)

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

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