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Eosinophils and exhaled Nitric Oxide (NO) levels are prominent features of asthma.  It is known that both exhaled NO and blood eosinophil counts (B-Eos) are markers of local and systemic eosinophil inflammation respectively, and are elevated in patients with the disease. However, little is known about the association of these markers with wheeze and asthma events.  Malinovschi et al [ J Allergy Clin Immunol 2013; 132(4):821-827 ] examined subjects from National Health and Nutrition Examination Survey 2007-2008 and 2009-2010 to determine individual and independent B-Eos and Fraction of Exhaled Nitric Oxide (FENO) levels in relation to wheeze, asthma diagnosis, and asthma events. From the cross sectional study, 12,408 subjects ranging from 6-80 years old were selected who had FENO measurements and blood differential counts.  The authors report that the prevalence of current asthma and wheeze increased progressively with FENO values and B-Eos values.  Furthermore, ther...

The prevalence of asthma is ubiquitous across the United States, but the major allergens of public health relevance that contribute to the disease vary across geographical regions.  Within inner cities, the 2 most common allergens are mouse and cockroach. Ahluwalia et al [ J Allergy Clin Immunol 2013; 132(4):830-835 ] sought to determine the relevant antigen(s) most highly associated with inner city asthma morbidity within Baltimore city. The motivation of their study was not only to aid in the management of asthma within the community but to assist in the reduction of levels of these antigens community wide.  The authors selected 144 children between 7 and 10 years old that had been clinically identified with asthma at least one year before the start of the study.  At the start of the study, they underwent skin prick tests and had clinical data collected at baseline and again at 3, 6, 9, and 12 months.  At the same time points, settled house dust samples were collec...

Keeping on the topic of natural killer cells, Jordan Orange, MD, PhD contributes a review on immunodeficiencies associated with NK cell dysfunction [ J Allergy Clin Immunol 2013; 132(3):515-525 ].  The author provides a concise review of NK cell biology, covering their intrinsic activities of cytotoxicity, tumor surveillance, and co-stimulation and signaling.  Orange points out that NK cell deficiency [NKD] is a subset of primary immunodeficiency diseases [PID] that is difficult to diagnose and treat because of the limited clinical information and testing available.  Like other PID, the author notes that NKD patients are characterized by a susceptibility to chronic and/or severe viral infections, especially herpes viruses.  Accurate diagnosis hinges on determining that the seminal deficiency is associated with NK cells, and that NKD is not secondary to other causes. The author provides an algorithm for identifying primary NKD.  Orange discusses the current class...

This month, Deniz et al. give an overview of current knowledge about natural killer cells [NK cells] and their interface with pathways and mechanisms of adaptive immunity, with attention to allergic disease processes [ J Allergy Clin Immunol 2013; 132(3):527-535 ].  The authors cover fundamentals of NK biology, such as their surface marker characterization, IFN-γ secretion, MHC class I interactions, phenotypes, tissue prevalence, cytokine profiles, and cytotoxicity to target cells.  NK cells are characterized by their cytotoxic activity through release of perforin and granzymes that are targeted at tumor cells, virally infected cells, and IgG antibody expressing cells, cytokine and chemokine secretion and signaling of adaptive immune cells, and co-stimulatory interaction with antigen presenting cells [APC] via IL-10 and TGF-β.   Deniz et al. note that NK chemokine secretion is particularly important in the co-localization and mutual maturation of dendritic cells [DC]...

In a review this month, Greer and co-authors present interesting information on just how much our health depends on the well-being and communal balance of the microscopic symbionts in our gastrointestinal tract [ Journal of Allergy and Clinical Immunology 2013; 132(2): 253-262 ].  They begin their review noting that, until fairly recently, immunity, metabolic functions and gut physiology had been studied as separate biological systems.  In light of growing evidence that the delineation between these is arbitrary, the authors point out that systems biology has developed new methods for investigating the interactions between the intestinal microbiota and immune and metabolic outcomes. Greer et al covers two broad categories, small intestine enteropathies and obesity with metabolic syndrome.  They describe current animal models used to study immunodeficiency enteropathies, celiac disease, inflammatory bowel disease, obesity and lipid metabolism dysregulation. The authors di...

Apoptosis was previously thought to be the only mode of regulated or programmed cell death in eosinophils, as necrosis was regarded as unregulated cell death.  However, Kano et al. , have discovered that the activated eosinophils, found in abundance in asthma and allergic disease, can die by means of a type of regulated necrosis in response to Siglec-8 ligation [ J Allergy Clin Immunol 2013; 132(2): 437-445 ]. Siglec-8 is a cell-surface receptor protein that is highly and selectively expressed by human eosinophils, as well as mast cells and basophils. The authors show that Siglec-8 ligation in the presence of IL-5 triggers necrosis in activated eosinophils in a reactive oxygen species (ROS) – dependent manner. Further, they explain why IL-5 promotes cell death in this system even though it is typically a pro-survival signal.  They demonstrate that ROS switch IL-5’s function from pro-survival to cell death enhancement by augmenting ERK phosphorylation and this serves as a decis...

Highlighting the role of innate immunity in the evolution of obesity and associated metabolic disorders, Jin and Flavell deliver a concise review of mechanisms involving pattern recognition receptors that produce pathology in liver, pancreas, brain and intestinal microbiota [ J Allergy Clin Immunol 2013; 132(2):287-294 ].  The authors provide a summary of the biology of the major types of pattern recognition receptors [PRR], with emphasis on toll-like receptors [TLR] and NOD-like receptors [NLR].  They discuss briefly their activity in response to pathogen infection and endogenous injury.  Several NLRs can coalesce into multiprotein complexes called inflammasomes which have proven to be important ly involved in the development of insulin resistance.  Jin and Flavell review PRR mechanisms in five critical physiologic areas: brain, pancreatic islet, and vascular inflammation, induction of peripheral insulin resistance, and disruption of intestinal microbiota homeos...