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• Current impact: H1N1 in asthma
• Cats with no dander and other “furry tales”
• Stem cell transplantation therapy for primary immunodeficiency
• The right influences
• A fragile fungal defense

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Current impact: H1N1 in asthma 

Every day, allergists are receiving telephone calls from asthmatic patients concerning fears of severe influenza A infection, asthma exacerbations, and advice for vaccination. Limited data are available on disease characteristics and outcomes of subjects with 2009 pandemic influenza A (H1N1). Both in children (CMAJ 2009, doi:10.1503/cmaj.091724) and adults (The ANZIC Influenza Investigators, N Engl J Med 2009;361:1925-34, and Jain et al, N Engl J Med 2009;361:1935-44), asthma appears to be a small risk factor for severe disease, with no clear relation to severity of asthma and not any greater risk for other chronic conditions, such as obesity or diabetes. Racial minorities are overrepresented among patients with severe infection. Indigenous populations from Australia, Canada, New Zealand, and other Pacific Islands have been found to have a 3 to 8 times higher rate of hospitalization and death associated with infection with the 2009 pandemic influenza A (H1N1) virus (La Ruche et al, Euro Surveill 2009;14:19366; MMWR Morb Mortal Wkly Rep, December 11, 2009). In these studies asthma was found to be one of the risk factors. Moreover, there are no reports on asthma exacerbations induced by influenza A. These new findings agree with the recent Clinical pearls article by Rank and Li (J Allergy Clin Immunol 2009;124:1123-6).

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Cats with no dander and other “furry tales” 

Cats with little or no Fel d 1? Get out! But that is exactly what Allerca Lifestyle Pets promised in 2004 when they opened for business. A December blog post on the-scientist.com (B. Grant) reported that the company is getting out of the business of accommodating persons with cat allergy who simply cannot live without the antigen vector. Seems the company had some difficulty delivering the hypoallergenic cats, literally, at the stupefying price of $9,000. There were also complaints that the Allerca cats caused the same degree of allergic reaction as any free-for-the-taking alley cat. In fact, authorities in The Netherlands took custody of 3 Allerca cats that were identified subsequently as “Savannah” cats by the breeder who sold them to Allerca. Seriously, how hard can it be to get cats to do what they do best: make more cats?

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Stem cell transplantation therapy for primary immunodeficiency 

Dr Morton Cowan, of the University of California San Francisco, has been awarded $6.25 million over 5 years to investigate hematopoietic stem cell therapy for pediatric primary immunodeficiency. The award came from the National Institute of Allergy and Infectious Diseases' Division of Allergy, Immunology, and Transplantation and Office of Rare Diseases. An international team of prominent allergists/immunologists are involved in this new 5-year prospective study of methods of stem cell transplantation, including Rebecca Buckley, MD; Jennifer Puck, MD; Luigi Notarangelo, MD; Thomas Fleisher, MD; Hans Ochs, MD; Fabio Candotti, MD; Charlotte Cunningham-Rundles, MD; Chaim Roifman, MD; and Jack Routes, MD. For more information, visit http://news.ucsf.edu/releases/ucsf-to-lead-new-nih-funded-consortium-for-studying-immune-disorders/.

We asked Dr Cowan for his thoughts about this new consortium: “The formation of the Primary Immune Deficiency Treatment Consortium (PIDTC) is a unique opportunity to bring together scientists and clinicians . . . with a special interest in treating children with rare inherited deficiencies of the immune system. Our objective is to study the use of hematopoietic cell therapy for 3 disorders: severe combined immune deficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease. We will use retrospective, cross-sectional, and prospective analyses to understand patient and transplant-related factors . . . that determine and/or predict outcome. We expect that these initial studies will form the basis for . . . randomized treatment trials that only a group such as the PIDTC could do . . . .”

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• Morton Cowan

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The right influences 

The glamorous airway players in the asthma-atopy arena have been bested by the parenchymal maintenance crew. Interstitial macrophages (IMs), in contrast to alveolar macrophages (AMs), have been characterized for the first time by Bedoret et al (J Clin Invest 2009;119:3723-38) as the driving force behind tolerance to harmless airborne allergens. Starting with the observation that endotoxin, which is associated with allergic asthma–induced T_H2 responses, does not illicit an allergic response in most persons, the authors discovered that IMs, but not AMs, suppressed the maturation and migration of lung dendritic cells (DCs) activated by endotoxin. Bedoret et al noted that IMs are found in close physical proximity to lung DCs, allowing for immediate response to DC activation, and mediated their inhibitory effects in an IL-10–dependent way. The authors proposed a new model of airway tolerance based on the IM's ability to prevent DC-associated T_H2 responses and suggested that asthma is a consequence of dysfunction in the IM's protective effects.

Fabrice Bureau, DVM, PhD, senior author on the article, provided this comment: “Our study is the first to demonstrate a regulatory role for lung IMs. In normal conditions these cells prevent airway allergy and thus maintain immune homeostasis in the lung by paralyzing pulmonary DCs, which are therefore unable to migrate to the draining lymph nodes and to induce T_H2 cell responses. This mechanism of action is of important biological significance [and] implies that harmless inhaled antigens are ignored (ie, absence of T-cell responses) rather than tolerated (ie, induction of antigen-specific regulatory T cells), as previously thought.”

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• Fabrice Bureau

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A fragile fungal defense 

Ferweda et al (N Engl J Med 2009;361:1760-7) have described a single nucleotide polymorphism (SNP) associated with recurrent mucocutaneous fungal infection in a family of Dutch ancestry. The index patient and her siblings, who were all homozygous for the SNP, had not only recurrent vaginal fungal infections but also onychomycosis. The authors characterized the mutation as a tyrosine→stop codon in the terminal exon coding for dectin-1. Their analysis revealed significantly decreased surface expression of the mutated dectin-1 receptor and decreased IL-6 production resulting from impaired β-glycan recognition by monocytes and macrophages. They noted that neutrophils from these patients killed Candida albicans as effectively as those from healthy control subjects, which protected them from invasive fungal infection. Because dectin-1 is expressed by epithelial cells, the authors suggested that this explained the cutaneous presentation of the clinical symptoms. Phylogenetic analysis identified this SNP as present in all African populations and most Western Europeans tested, but not in Asians, supporting an ancient origin for the mutation.

Senior author Mihai Netea, PhD, MD, had this to add: “The finding of dectin-1 stop polymorphisms that influence susceptibility to mucocutaneous fungal infections has several important conceptual consequences. First, it demonstrates that dectin-1 is a nonredundant host mechanism against infections . . . of mucosal surfaces. Second, these findings also show that alternative mechanisms . . . compensate in the absence of dectin-1 in the case of disseminated fungal infections . … Finally, these new results show that… mechanisms to protect against fungal infections have been largely conserved by evolution between mice and human subjects, which is not necessarily the case for other microbes.”

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• Mihai Netea