Volume 1.31 | Oct 15

Human Immunology News 1.31 October 15, 2013
Human Immunology News
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An ACT1 Mutation Selectively Abolishes Interleukin-17 Responses in Humans with Chronic Mucocutaneous Candidiasis
Investigators report a biallelic missense mutation (T536I) in the adaptor molecule ACT1 in two siblings with chronic mucocutaneous candidiasis. The mutation, located in the SEFIR domain, abolished the homotypic interaction of ACT1 with interleukin (IL)-17 receptors, with no effect on homodimerization. The patients fibroblasts failed to respond to IL-17A and IL-17F, and their T cells to IL-17E. [Immunity] Abstract
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T Cells from Autoimmune Patients Display Reduced Sensitivity to Immunoregulation by Mesenchymal Stem Cells: Role of IL-2
Scientists investigated the ability of healthy donor derived mesenchymal stem cells (MSCs) to inhibit the proliferation of T cells from two pathophysiologically different autoimmune diseases (AIDs): Multiple Sclerosis and Myasthenia Gravis. They showed that MSC-induced inhibition of interferon-γ production and surface expression of the CD3, CD4 and CD28 receptors by activated lymphocytes was similar in the AID patients and healthy controls. [Autoimmun Rev] Abstract

The Majority of Patients with Long-Duration Type 1 Diabetes Are Insulin Microsecretors and Have Functioning Beta Cells
Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. The authors aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus. [Diabetologia] Full Article | Press Release

Epstein-Barr Virus Co-Infection in Children Boosts Cytomegalovirus-Induced Differentiation of Natural Killer Cells
Scientists found that Epstein-Barr virus (EBV) co-infection selectively influenced the natural killer (NK)-cell compartment of cytomegalovirus (CMV)-seropositive (CMV+) children. Co-infected children had significantly higher proportions of peripheral-blood NKG2C+ NK cells than CMV+EBV children. [J Virol] Abstract

Activation of Human Basophils by Combined Toll-Like Receptor- and FcεRI-Triggering Can Promote T Helper 2 Skewing of Naive T Helper Cells
The activation of basophils via Toll-like receptors (TLRs) in combination with activation via IgE was studied, as well as its effect on T helper cell skewing. Using quantitative PCR, the authors demonstrated the presence of mRNA for TLRs 1-8 in humanan basophils. [Eur J Immunol] Abstract

IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID
Researchers addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed common variable immunodeficiency (CVID) patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. [PLoS One] Full Article

Persistent Changes in Circulating and Intestinal γδ T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Celiac Disease
Investigators used multi-color flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with celiac disease and healthy matched controls. [PLoS One] Full Article

Cutting Edge: IL-10-Producing Regulatory B Cells in Early Human Pregnancy
The function of IL-10 producing regulatory B cells during gestation is unknown. Here, the authors aimed to understand their participation in early pregnancy. CD19+CD24hiCD27+B cell frequency, measured by flow cytometry, increased with pregnancy onset but not in the case of spontaneous abortions. [Am J Reprod Immunol] Abstract

DNA Methylation Modulates HRES1/p28 Expression in B Cells from Patients with Lupus
Since previous studies have demonstrated that CD4+ T cells and B cells from systemic lupus erythematosus patients are defective in their ability to methylate their DNA upon antigen stimulation, scientists investigated whether DNA demethylation affects the transcription of HRES-1 in B cells. [Autoimmunity] Abstract

High Degree of Correlation between Whole Blood and PBMC Expression Levels of miR-155 and miR-146a in Healthy Controls and Rheumatoid Arthritis Patients
Researchers sought to determine whether microRNA (miRNA) levels detected in whole blood samples correlated with those detected in simultaneously isolated peripheral blood-derived mononuclear cells (PBMC) from the same individuals, thus establishing the feasibility of using whole blood as a viable clinical material for monitoring miRNA expression in rheumatoid arthritis and other disorders. [J Immunol Methods] Abstract

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Treatment of Systemic Lupus Erythematosus: New Therapeutic Avenues and Blind Alleys
Despite rapid accumulation of knowledge about complex immune dysregulation in systemic lupus erythematosus and major primary lupus syndromes, and a plethora of promising new treatments reaching preclinical and early clinical studies, advanced-phase trials of new biologic agents have repeatedly failed to achieve their clinical end points. It is possible that none of these agents work, but the accuracy of this suggestion is as unclear as the case for efficacy, owing to issues in the design of studies and the opacity of the data that have resulted. [Nat Rev Rheumatol] Abstract

IgE-Based Immunotherapy of Cancer: Challenges and Chances
This review highlights the latest developments toward IgE-based immunotherapy of cancer. Possible mechanisms and safety aspects of IgE-mediated tumor cell death are discussed with special focus on the attracted immune cells. [Allergy] Abstract

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Clinical Trial Harnesses Power of Natural Killer Cells to Treat Neuroblastoma
For the first time, scientists will combine natural killer cell therapy with an immunocytokine to target children with relapsed/refractory disease including those with bulky tumors. Solving Kids’ Cancer and The Catherine Elizabeth Blair Memorial Foundation awarded a $136,000 grant to support the novel immunotherapy clinical trial for childhood cancer. [Solving Kids’ Cancer] Press Release

Lupus Research Institute Announces New Global Research on Fundamental Causes of Lupus
The Lupus Research Institute (LRI) announced recipients of its 2013 Distinguished Innovator Award, taking the organization across the globe to support highly innovative studies on two continents. [PR Newswire Association LLC] Press Release

Immune Pharmaceuticals Announces Changes to Its Board of Directors
Immune Pharmaceuticals Inc. announced that Rene Lerer, M.D., Executive Chairman of Magellan Health Services, and Daniel Kazado, Senior Advisor to Melini Capital, have agreed to join the Company’s Board of Directors. [Immune Pharmaceuticals Inc.] Press Release

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NEW Asia Pacific Congress of Allergy, Asthma and Clinical Immunology (APCAACI) 2013
November 14-17, 2013
Taipei, Taiwan

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NEW Research Fellow – Cellular Immunity in Type 1 Diabetes (King’s College London)

NEW Postdoctoral Fellow – Immunotherapy (Washington University School of Medicine)

PhD Fellowship – Chronic Vagus Nerve Stimulation as Therapy for Colitis (KU Leuven)

Postdoctoral Position – Autoimmunity (University of Chicago)

Postdoctoral Scientist – Melanoma Biology (Gustave Roussy Cancer Institute)

PhD Research Position – Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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