The Editors' Choice

Article Outline

• Use of sublingual immunotherapy in stinging insect allergy
• Breast-feeding does not increase risk of asthma or atopy in childhood
• Exploring the antioxidant system in asthma
• Modulation of TIM4 in dendritic cells as a peanut allergy strategy
• Staphylococcus aureus lives in the skin of patients with atopic dermatitis because their skin cells do not kill it
• How common airway viruses trigger eosinophilic inflammation
• Copyright

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Use of sublingual immunotherapy in stinging insect allergy 

Sublingual immunotherapy (SLIT) has been reported to be effective in conditions other than respiratory allergy, such as food allergy and atopic dermatitis. Nevertheless, no attempt has been made thus far to use it in stinging insect allergy. Severino et al (p 44) performed a double-blind, placebo-controlled trial to assess whether SLIT might work in hymenoptera allergy. Because this was a proof-of-concept trial, only monosensitized patients with large local reactions due to honeybee stings were enrolled. Large local reactions were evaluated by sting challenges performed before and after treatment. SLIT (or placebo) was given for 6 months at a dose empirically chosen 5 times greater than in subcutaneous immunotherapy. Thirty adult patients were enrolled; 26 completed, and no side effect was reported. The median of the peak diameter of the local reaction significantly decreased in the active group (P = .014), with no change in the placebo group (see Figure). The reduction of the diameter was greater than 50% in 57% of patients. A significant increase in IgG4 was also seen in the active group. The authors conclude that SLIT might be of benefit in hymenoptera allergy and that this deserves further study. In particular, dose-finding trials and trials in patients with systemic reactions are mandatory.

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• Peak maximal diameter of the large local reactions at the sting challenge before and after treatment in the 2 groups.

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Breast-feeding does not increase risk of asthma or atopy in childhood 

Although many studies confirm that breast-feeding protects against the development of wheezing illness in early childhood, some recent data suggest that it might increase the risk of atopy and asthma at later ages. Complicating the picture, recent data suggest that reverse causation (mothers altering breast-feeding on the basis of atopic symptoms in the infant; see Figure) could bias studies. There are relatively few large prospective studies with objective measures of asthma and allergy outcomes in later childhood. Elliott et al (p 49) therefore examined the role of breast-feeding in both early wheezing and later asthma outcomes, including objective measures of atopy and bronchial hyperresponsiveness, and adjusted for possible reverse causation using prospective data from the large Avon Longitudinal Study of Parents and Children birth cohort. Breast-feeding protected against early wheezing but had no deleterious effects on atopy, bronchial hyperresponsiveness, or asthma diagnosis at the age of 7 years. The authors also found no evidence that breast-feeding increased the risk of these conditions in subsets defined by other factors, including maternal atopy or asthma, parental smoking, and gender. The tendency of wheezing children to be breast-fed longer than nonwheezing children did not bias the results. This study should reassure new mothers that breast-feeding will not increase the risk of asthma or allergies in their babies.

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• Wheezing babies are breast-fed for longer periods than nonwheezing babies.

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Exploring the antioxidant system in asthma 

The balance between oxidant stress and antioxidant defense systems is a crucial factor for many lung diseases, including asthma. As reported in this issue, Sackesen et al (p 78) determined the levels of enzymatic antioxidants superoxide dismutase and glutathione peroxidase and nonenzymatic antioxidants ascorbic acid, α-tocopherol, lycopene, and β-carotene in children with asthma and healthy children. The study confirms the existence of increased oxidative burden in asthma and further shows that the plasma levels of all components of the enzymatic and nonenzymatic antioxidants are significantly lower in asthmatic children than in healthy controls. In addition, the study investigates a new aspect of the oxidative stress and shows that amino acids involved in the synthesis of an important antioxidant, glutathione, and amino acids that are susceptible to oxidative stress are lower in asthmatic children than in controls. The authors conclude that childhood asthma is associated with a very strong impairment of various components of both enzymatic and nonenzymatic defense systems and that antioxidant treatment approaches targeting a single component of the oxidant/antioxidant system are therefore unlikely to be successful in asthma.

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Modulation of TIM4 in dendritic cells as a peanut allergy strategy 

As reported in this issue, Feng et al (p 55) aimed to elucidate the mechanisms of peanut allergy mediated by microbial products and dendritic cells and its relationship to T-cell immunoglobulin and mucin domain molecule 4 (TIM4). Mouse bone marrow–derived dendritic cells (BMDCs) were generated and exposed to cholera toxin (CT) or/and peanut extract (PE) for 24 hours and then adoptively transferred to naive mice. After re-exposure to specific antigen PE, the mice were killed; intestinal allergic status was then determined (see Figure). Increased expression of TIM4 and costimulatory molecules was detected in BMDCs after concurrent exposure to CT and PE. Adoptively transferred CT/PE-conditioned BMDCs resulted in increases in serum PE–specific IgE and skewed T_H2 polarization in the intestine. Oral challenge with specific-antigen PE induced mast cell activation in the intestine. Treating with Toll-like receptor 4 small interfering RNA abolished increased expression of TIM4 and costimulatory molecules by BMDCs. Pretreatment with anti-TIM1 or anti-TIM4 antibody abolished PE-specific T_H2 polarization and allergy in the intestine. Concurrent exposure to microbial product CT and food antigen PE increases TIM4 expression in DCs and promotes DC maturation that plays an important role in the initiation of PE-specific T_H2 polarization and allergy in the intestine. Modulation of TIM4 production in DCs represents a novel approach to the treatment of peanut allergy.

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• Adoptively transferred DCs in the intestine.

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Staphylococcus aureus lives in the skin of patients with atopic dermatitis because their skin cells do not kill it 

People with eczema (atopic dermatitis) are often bothered by bacteria on the skin. Kisich et al (p 62) investigated the reasons that the skin of people with eczema allows S aureus to persist, whereas the skin of people without eczema rarely permits such colonization. The authors previously showed that the skin cells (keratinocytes) of healthy people rapidly killed the S aureus that contacted them using the endogenous antibiotic β-defensin-3. In this article, they have shown that the keratinocytes of people with eczema kill S aureus poorly despite the fact that they contain the same amount of β-defensin-3 as normal cells. The cells from patients with eczema have trouble killing the bacteria because they cannot move intracellular β-defensin-3 onto the bacteria at the cell surface. The block in movement of the defensin can be reproduced by exposing normal keratinocytes to the T_H2 cytokines, IL-4 and IL-13. Defensin mobilization and killing of S aureus by the skin of patients with eczema can be restored by blocking the action of IL-4 and IL-13 with antibodies to those proteins. This suggests that strategies to reduce IL-4 and IL-13 could help patients eliminate S aureus.

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• Destruction of S aureus by normal skin (B) but not by eczematous skin (A).

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How common airway viruses trigger eosinophilic inflammation 

Asthma exacerbation occurs frequently after common cold virus infections. Eosinophils are important components of the inflammatory response of subjects with asthma and have been associated with asthma exacerbation. Davoine et al (p 69) report a possible immune mechanism linking airway virus infections and eosinophil mediator release. Parainfluenza, respiratory syncytial, or rhinovirus was cocultured with human antigen-presenting cells (APCs) (macrophages and dendritic cells), T cells, and eosinophils. The data suggest that viruses can induce the release of eosinophil peroxidase but only when coincubated in the presence of APCs and proliferating T cells. UV-inactivated virus induced eosinophil mediator release, implying that T cells might be responding to the viruses because of their antigenicity rather than because of their infectivity. This was further confirmed by the fact that the proliferating T cells were CD4⁺ (but not CD8⁺) that had an increased expression of CD25 (IL-2 receptor) as well as elevated expression of CD45RO (memory T-cell marker). The article therefore proposes that if effector cells such as eosinophils are abundant in the airways before a virus infection, viral presentation to virus antigen-specific memory CD4⁺ T cells might induce eosinophil-mediated asthma exacerbation.