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BACKGROUND The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) and severe reductions of(More)
OBJECTIVE To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. METHODS Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan-Meier survival curves for each JIA category were used to estimate(More)
Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans. A major impediment to advances in understanding, preventing, and curing T1D has been the inability to "see" the disease initiate, progress, or regress, especially during the occult phase. Here, we report the development of a(More)
Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved(More)
Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete(More)
BACKGROUND Antibiotic desensitization is an option for patients with suspected IgE-mediated antibiotic allergy when no other alternative exists for treating life-threatening bacterial infections. However, there are limited data describing the outcomes of this procedure with newer, commonly used antibiotics. OBJECTIVE To evaluate the safety and utility of(More)
Cardiac ischemia causes a rapid decline in mechanical performance and, if prolonged, myocardial cell death occurs on reperfusion. The early decline in mechanical performance could, in principle, be caused either by reduced intracellular calcium release or by reduced responsiveness of the myofibrillar proteins to calcium. It is now known that intracellular(More)
Novel therapies to target lung inflammation are predicted to improve the lives of people with cystic fibrosis (CF) but specific antiinflammatory targets have not been identified. The goal of this study was to establish whether TLR5 signaling is the key molecular pathway mediating lung inflammation in CF, and to determine whether strategies to inhibit TLR5(More)
BACKGROUND The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. OBJECTIVE To explore associations of infant gut microbiota and food sensitization. METHODS Food sensitization at 1 year(More)
Variability in TLR function influences susceptibility to infectious as well as immune-mediated diseases. Given the outbred nature of humans, identifying functional Toll-like receptor variability and its role in clinical disease requires such analysis to be conducted in large, often multi-centered cohorts. Yet the technically complex measurements involved in(More)