Receptor protects against allergies, asthma

The scientists found that the receptor, dectin-1, recognizes a protein found in house dust mites, cockroaches, shellfish and other invertebrates, and responds by suppressing immune reactions to these common triggers of allergy and asthma. This protective mechanism is dramatically impaired in people who have asthma or chronic sinusitis due to dust-mite sensitivity. Everyone is exposed to these substances, yet most don't have allergic responses to them.The discovery also hints that while dectin-1 protects against dust-mite and other invertebrate-related allergic responses, there may be additional, undiscovered receptors that suppress allergic responses to pollens and other airborne and dietary allergens. Dectin-1 previously has been studied as a receptor that recognizes structures on fungi and other microbes and triggers immune responses to them. There have even been suggestions that dectin-1 helps trigger allergic responses to dust mites. The lead researcher found to their surprise that the airways of these dectin-1-deficient mice were more prone to inflammation after exposure to dust mites compared to otherwise identical mice whose airway cells expressed dectin-1 normally. Blocking dectin-1 with antibodies had the same allergy-promoting effect. Thus, dectin-1 protects against dust-mite allergies rather than promoting them. The scientists determined that dectin-1, in addition to its fungus- and other pathogen-detecting duties, directly recognizes a protein called tropomyosin that is found in house dust mites and other invertebrates. Tropomyosin has previously been implicated as a possible trigger for asthma and shrimp allergies. The experiments indicated that when dectin-1 recognizes tropomyosin in house dust mites, shrimp or other common allergy-triggering species it suppresses airway cells' production of an immune molecule, IL-33, which otherwise would promote an allergic response by immune cells. Underscoring the relevance to humans, nasal and bronchial cells from people who suffer from asthma or chronic rhinosinusitis (nasal congestion/sniffles) due to dust-mite sensitivity, and found that on average these cells had a markedly lower expression of the dectin-1 gene. The lead researcher suggest that people who have sufficient dectin-1 in the cells that line their airways won't experience an allergic response when exposed to airborne dust mites or related allergens but people with a defect in dectin-1 expression will lack this protection. The findings point to the possibility of boosting dectin-1 levels, or otherwise restoring its protective effect, as a new therapeutic strategy against asthma and allergies that are related to dust mites, shrimp or other invertebrate triggers.

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Researchers reported for the first time that a genetic biomarker may be able to help predict the severity of food allergy reactions. Currently there is no reliable or readily available clinical biomarker that accurately distinguishes patients with food allergies who are at risk for severe life-threatening reactions versus more mild symptoms. Researchers found that the presence of an enzyme isoform called α-tryptase, which is encoded by the TPSAB1 gene, correlates with increased prevalence of anaphylaxis or severe reaction to food as compared to subjects without any α-tryptase. Determining whether or not a patient with food allergies has α-tryptase can easily be done in clinical practice using a commercially available test to perform genetic sequencing from cheek swabs. If the biomarker is detected, this may help us understand that the child is at a higher risk for a severe reaction or anaphylaxis from their food allergy and should use their epinephrine auto-injector if exposed to the allergen. Their findings also open the door to developing an entirely new treatment strategy for food allergies that would target or block α-tryptase. This is an exciting first step and more research is needed. Tryptase is found mainly in mast cells, which are white blood cells that are part of the immune system. Mast cells become activated during allergic reactions. Increased TPSAB1 copy number which leads to increased α-tryptase is already known to be associated with severe reactions in adults with Hymenoptera venom allergy (or anaphylaxis following a bee sting). The study included 119 participants who underwent TPSAB1 genotyping, 82 from an observational food allergy cohort at the National Institute of Allergy and Infectious Diseases (NIAID) and 37 from a cohort of children who reacted to peanut oral food challenge at Lurie Children's. Researchers need to validate preliminary findings in a much larger study, but these initial results are promising.

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                             Sleep-wake therapy gives new hope for teens with depression

Promoting healthy sleep in teen night owls brings adolescents' biology and school demands in alignment. School systems aren't built for kids who fall asleep and wake up late, the so-called "night owls," which may help explain why this group of teens is more prone to depression. Now, researchers have found a way to help these kids adjust to their natural sleep-cycle rhythms while still fulfilling their school responsibilities. The findings are a welcome sign for adolescents with depression, who are more likely than most to report staying up late. The key to success with the current intervention was teaching the night owls to structure their lives so they could sleep as late as possible, while gently training their bodies to fall asleep a little earlier. At the beginning of the study, all of the teens scored at least 40 on the Children's Depression Rating Scale, a level that indicates clinically significant depression. A score of 28 or lower indicates remission. Six months after the treatment, the intervention group's average score had fallen to 21.67, compared to 32.5 for the group that received the healthy lifestyle intervention. A larger study has since been funded by the National Institute of Mental Health, and it will be open for enrollment to 200 teens in the Bay Area this fall. About 3 million adolescents have at least one major depressive episode in a given year, and about 40% don't respond to treatment. Teens whose natural tendencies are to fall asleep later and wake up later are at higher risk for recurrent depression, more severe depression, suicidality and poor antidepressant response, research shows.

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