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In addition to having a nonfunctional NADPH oxidase, activated phagocytes from patients with chronic granulomatous disease (CGD) and gp91phox-/- mice (modeling X-linked CGD) lack oxidant production from mitochondria, as reported by authors Fernandez-Boyanapalli et al ( http://www.jacionline.org/article/S0091-6749%2814%2901576-0/abstract ) . Specifically, neutrophils and monocytes from blood, as well as recruited neutrophils and macrophages from inflamed tissues of CGD mice, failed to produce mitochondrial oxidants when activated. Deficient mitochondrial oxidant production was shown to contribute to impaired bactericidal activity against Staphylococcus aureus and Burkholderia cepacia in vitro. Importantly, the researchers demonstrated that mitochondrial oxidant production was restored (see Figure) following short-term treatment of CGD mice with pioglitazone, a PPAR? agonist approved for treatment of type 2 diabetes. Pioglitazone is known to induce metabolic changes that mimic “starvatio...

Psoriasis, a chronic immune-mediated inflammatory skin disease, affects approximately 2% of the global population. Eighty to ninety percent of patients have plaque psoriasis, and the extent of the affected surface areas of the body and the degree of redness, hardening, and scaling of the skin define its severity. In addition to its negative effect on well-being and quality of life, moderate-to-severe psoriasis has comorbidities including increased risk of heart disease and stroke. Approximately 25% of psoriasis patients have moderate-to-severe disease. Genome-wide association studies have previously linked a variant in the genes for the IL-23 receptor and the p19 subunit of IL-23, or IL-23A, to psoriasis susceptibility. BI 655066 is a fully-human IgG 1 mAb selective for IL-23A. In this phase I proof-of-concept study, Krueger et al evaluated the results of administering a single-rising-dose of BI 655066 to patients with moderate-to-severe plaque psoriasis ( J Allergy Clin Immunol 2015 ...

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review by Konradsen et al, research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components ( J Allergy Clin Immunol 2015; 135: 616-625 ). Exposure to allergens ...

Recent years have seen a tremendous acceleration of knowledge in the field of glycobiology, revealing many intricacies and functional contributions that were previously poorly appreciated or even unrecognized. This review by Bochner and Zimmermann highlights several topics relevant to glycoimmunology in which mammalian and pathogen-derived glycans displayed on glycoproteins and other scaffolds are recognized by specific glycan-binding proteins (GBPs), leading to a variety of proinflammatory and anti-inflammatory cellular responses ( J Allergy Clin Immunol 2015; 135: 598-608 ). Their main focus is on 2 families of GBPs, sialic acid–binding immunoglobulin-like lectins (siglecs) and selectins, which are involved in multiple steps of the immune response, including distinguishing pathogens from self, cell trafficking to sites of inflammation, fine-tuning of immune responses leading to activation or tolerance, and regulation of cell survival. Importantly for the clinician, accelerated rates ...

Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal; thus, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Recently, Steinke and colleagues have identified a novel IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal) ( J Allergy Clin Immunol 2015; 135: 589-596 ). IgE to alpha-gal has been associated with two distinct forms of anaphylaxis: i) immediate onset anaphylaxis during first exposure to intravenous cetuximab which is a monoclonal antibody specific for the epidermal growth factor receptor (EGFR), and ii) delayed onset anaphylaxis 3-6 hours after ingestion of mammalian food products (e.g., beef and pork). Results from their studies and those of others strongly suggest that tick bites are a cause, if not the only significant cause, of IgE antibody responses to alpha-gal in the southern, eastern and central United States, Europe, Australia and parts of Asia. In 2004, ...