News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2017)

Infection with respiratory syncytial virus (RSV) during infancy has been linked to increased risk for later onset of asthma. Additionally, prophylactic use within the first year of life of palivizumab, an mAb directed against the RSV fusion glycoprotein, protects against chronic wheezing through the third year of life. In this prospective, multicenter, case-control study, Mochizuki et al (Am J Respir Crit Care Med 2017; https://doi.org/10.1164/rccm.201609-1812OC) examined the effect of prophylactic treatment with palivizumab during the first year of life on the incidence of asthma at age 6 years. Of the 444 preterm infants between 33 and 35 weeks of gestational age at 52 centers in Japan who were enrolled in the study, 349 received 3 or more doses of palivizumab, whereas 95 control infants did not receive any palivizumab treatment. At 6 years of age, there was no statistical difference in the rate of asthma in infants treated with palivizumab compared with control subjects. Furthermore, between the palivizumab treatment and control groups, there were no statistically significant differences in peripheral blood mean total IgE and specific IgE levels or in the incidence of allergic diseases. Prophylactic palivizumab treatment caused a 2-fold decrease in the incidence of chronic wheezing. The results demonstrate that palivizumab prophylaxis decreases chronic wheezing but does not prevent atopic asthma in early childhood.Palivizumab prophylaxis decreases chronic wheezing but does not prevent atopic asthma in early childhood Palivizumab prophylaxis decreases chronic wheezing but does not prevent atopic asthma in early childhood We asked author Hiroyuki Mochizuki, MD, PhD, of Tokai University School of Medicine, Tokyo, Japan, to comment on this study. He writes, “A significant proportion of recurrent wheeze in children up to age six might be associated with RSV infection, whereas atopic asthma is probably not due to RSV.” The skin epithelium acts as an important barrier to protect the body from environmental insults. In response to injury, the skin epithelium must initiate both repair and proinflammatory responses. Kashiwagi et al (Nat Immunol 2017;18:334-43; https://doi.org/10.1038/ni.3661) examined in mice the molecular mechanisms regulating epithelial cells and downstream effects on immune responses. Chromatin remodeling nuclear protein Mi-2 maintains skin homeostasis. Genetic deletion of Mi-2 induced skin inflammation, including keratinocyte hyperplasia and immune cell infiltration. This inflammatory response was mediated at least in part through overproduction of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP), which activates dendritic cells to induce TH2 polarization of naive CD4+ T cells. However, TSLP also promoted resolution of inflammation through direct activation of regulatory T cells. The authors concluded that skin keratinocyte–derived TSLP exhibits both proinflammatory and immunosuppressive functions.Skin keratinocyte–derived TSLP exhibits both proinflammatory and immunosuppressive functions. Skin keratinocyte–derived TSLP exhibits both proinflammatory and immunosuppressive functions. The immune system uses finely controlled responses of a diverse array of specialized cell types to maintain protection against pathogens. This coordination is mostly achieved through release of proteins that activate surface receptors present on other cells. However, the molecular details of how various immune cells interact have not been examined by using broad-spectrum, biological network–based approaches. To characterize such interactions, Rieckmann et al (Nat Immunol 2017; https://doi.org/10.1038/ni.3693) used cutting-edge mass spectrometry–based techniques to determine the proteomes of 28 different immune cell types derived from human donors at baseline and under specific activation conditions. Additionally, they developed novel bioinformatics analyses to determine intercellular information exchange networks. The authors identify previously unknown intercellular communications, including that activated memory B cells secrete the hormone resistin and that CD4+ memory T cells respond to IL-34. Based on this work, the authors have identified immune cell–specific communication networks and created a publically available database (http://www.immprot.org) for future study of intercellular communications within the immune system. This resource should prove especially useful for the study of interactions between immunocytes within disease contexts. Figure attribution to user Janislan15 (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0), via Wikimedia Commons].The authors have identified immune cell–specific communication networks The authors have identified immune cell–specific communication networks A major gap in allergen-specific immunotherapy is the minimal effective duration of treatment with sublingual immunotherapy (SLIT). Three years of SLIT induces sustained tolerance for at least 2 years after treatment has stopped. In this randomized, double-blind study Scadding et al (JAMA 2017;317:615-25; https://doi.org/10.1001/jama.2016.21040) tested the efficacy of 2 years of SLIT to grass pollen in adults with allergic rhinitis. Thirty-six subjects received 2 years of daily SLIT with grass pollen allergen, whereas 34 subjects received placebo. Additionally, 36 subjects received monthly subcutaneous immunotherapy without concurrent SLIT. One year after cessation of treatment, efficacy was tested by using the Total Nasal Symptom Score at 0 to 10 hours after a nasal allergen challenge. Although both treatments were effective compared with placebo at year 2, there was not a statistically significant improvement in Total Nasal Symptom Scores in patients treated with SLIT compared with those receiving placebo at year 3. Similarly, subcutaneous immunotherapy did not show efficacy compared with placebo at year 3. These results suggest that 2 years of SLIT is insufficient for long-term clinical benefit and support the current practice of maintaining SLIT.Two years of SLIT is insufficient for long-term clinical benefit Two years of SLIT is insufficient for long-term clinical benefit We asked author Stephan Durham, Mb Bchir, MD, FRCP, of Imperial College London, UK, to comment on the study. He writes, “In this Immune Tolerance Network, NIAID-sponsored clinical trial, both sublingual and subcutaneous immunotherapy were effective, whereas two years treatment was insufficient for long-term tolerance.”News items were written by medical writer Jared Travers.Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com. News items were written by medical writer Jared Travers. Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.