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Member Society Spotlight: Health and Environmental Sciences Institute

The Health and Environmental Sciences Institute (HESI) is a non-profit institution, founded in 1989, whose mission is to engage scientists from academia, government and industry to identify and resolve global health and environmental issues. HESI provides the structure, credibility, and management necessary for successful collaboration amongst scientists from academia, government, research institutes, foundations, and industry to identify and resolve global health and environmental issues.


FOCIS Congratulates Yale as an Outstanding FOCIS Center of Excellence in their $14.5 million Collaboration with AbbVie

With the goal of advancing the understanding of the autoimmune and inflammatory diseases, and trying to find new and better treatments, Yale School of Medicine (YSM) has entered into a research partnership with the global pharmaceutical company AbbVie. Formed in 2013 when Abbott Laboratories divided into two companies, this North Chicago, Illinois based company will provide $14.5 million over a five-year period to fund research led by the Yale faculty.


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FOCIS ePub Header

September 17, 2014

EditorAndrew H. Lichtman, MD, PhD, Brigham & Women's Hospital
Editorial Board: Abul K. Abbas, MD, University of California, San Francisco | Carla J. Greenbaum, MD, Benaroya Research Institute | Andrew H. Lichtman, MD, PhD, Brigham & Women's Hospital

Highlights from Recent Literature

A Surprising Immune Etiology for Narcolepsy

A review of De la Herrán-Arita, et al., CD4+ T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy. Science Translational Medicine 5, 216ra176 (2013). PMID: 24353159

Type I narcolepsy is a lifelong disorder characterized by sleepiness, aplexy, and rapid transition from wakefulness to REM sleep. Type I narcolepsy is strongly associated with HLA DQ0602 and results from the loss of the approximately 70,000 posterior hypothalamus neurons that produce the wake promoting neuropeptide hypocretin.


Highlights from Clinical Immunology, Official Journal of FOCIS

A SLAP in the Face of Autoimmunity

A review of Peterson L. et al. SLAP Deficiency Decreases DsDNA Autoantibody Production. Clinical Immunology 150, 201-209, 2014 PMID: 24440645

Src-like adaptor protein (SLAP) down-regulates BCR signaling by promoting c-Cbl-mediated ubiquitin ligation of BCR complex proteins, leading to their degradation. This SLAP function reduces BCR levels in developing B cells. The authors investigated if SLAP deficiency could enhance central B cell tolerance by increasing BCR signaling in developing autoreactive B cells leading to deletion or receptor editing. They tested the effects of SLAP-deficiency using two models of anti-dsDNA autoimmunity. The first model uses vaccination with a peptide mimeotope, which induces an anti-dsDNA response in mice, and glomerular deposition of Ig. The second model is a Ig heavy chain transgenic mouse (56R), in which the transgene was cloned from a B cell derived from autoimmune MRL/lpr mouse. The 56R mouse spontaneously produces anti-dsDNA IgG autoantibodies with various light chains.


Developments in Basic Immunology and Novel Therapies

Old Diseases in a New Bottle: IgG4-related Disease

Shiv Pillai, MD, PhD, Massachusetts General Hospital, Harvard Medical School

Over the past decade a new disease entity has attracted a lot of interest. Patients presenting with tumescent, often painful, lesions affecting a variety of anatomic sites, initially often thought to have a malignant disease, have had biopsies analyzed that reveal a constellation of features that lead to a diagnosis of an entity now called IgG4-related disease or IgG4-RD. The histological features include storiform fibrosis, obliterative phlebitis, and the presence of a lymphoid and plasmacytic cell infiltrate in which forty percent or more of the IgG expressing plasma cells stain for the IgG4 isotype. Plasma levels of IgG4 may also be elevated.


Human Immunophenotyping Update

Data Normalization: How to Handle Batch Effects in Large Studies

Holden T. Maecker, PhD, Stanford University
Janet Siebert, MS, MEd, CytoAnalytics, Inc.

There is a theme among those doing translational immunology that "mice are easy, humans are hard". One of the more subtle ways that this truism plays out is in the greater need to deal with batch effects in human studies. Partly because of genetic heterogeneity, human studies often involve more subjects than a typical animal study. Also, while animal studies can be manipulated so that all the animals reach a particular endpoint at the same time, human studies often cannot. Thus, in situations requiring fresh samples, one must perform the human assays longitudinally. For both of these reasons (number of subjects and the occasional need for real-time assays), one often faces the prospect of comparing human data across multiple "runs" or batches. Given the variability of many immune monitoring assays, this generally results in some run-to-run variability, or "batch effect", and the consequent need for normalization of data across batches (1). Here, we will discuss some high-level considerations that should be given when designing studies for downstream normalization, and what normalization options are available for various study designs.


Selected Recent Clinical Trial Results
  • Systemic Lupus Erythematosus
  • Relapsing-remitting Multiple Sclerosis
  • Crohn's Disease (CD)




Thank you to the 2013 FOCIS Corporate Council:

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