Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by difficulties in communication, cognitive and learning deficits, as well as stereotypic behaviors. For the majority of cases there are no reliable biomarkers or distinct pathogenesis. However, increasing evidence indicates ASD may be associated with some immune dysregulation, and may have a neuroimmune component. We recently showed that the peptide neurotensin (NT) is increased in autistic children. We now show that NT induces release of extracellular mitochondrial DNA (mtDNA) that could act as "autoimmune" trigger. We further show that serum from young autistic patients contains mtDNA (n = 20; cytochrome B, p = 0.0002 and 7S, p = 0.006), and anti-mitochondrial antibody Type 2 (n = 14; p = 0.001) as compared to normally developing, unrelated controls (n = 12). Extracellular blood mtDNA and other components may characterize an autistic endophenotype and may contribute to its pathogenesis by activating autoimmune responses.

Neurotensin is increased in serum of young children with autistic disorder.

Autism spectrum disorders (ASD) are a group of pervasive neurodevelopmental disorders diagnosed in early childhood. They are associated with a set of "core symptoms" that include disabilities in social interaction skills, verbal and non-verbal communication, as well as repetitive and stereotypic behaviors. There is no definite pathogenetic mechanism or diagnostic tests. Many children with ASD also have "allergic-like" symptoms, but test negative implying mast cell activation by non-allergic triggers. We measured by Milliplex arrays serum levels of 3 neuropeptides that could stimulate mast cells in children with autistic disorder (n = 19; 16 males and 3 females; mean age 3.0 ± 0.4 years) and healthy, unrelated controls (n = 16; 13 males and 3 females; mean age 3 ± 1.2 years). Only neurotensin (NT) was significantly increased from 60.5 ± 6.0 pg/ml in controls to 105.6 ± 12.4 pg/ml in autistic disorder (p = 0.004). There was no statistically significant difference in the serum levels of ß-endorphin or substance P (SP). NT could stimulate immune cells, especially mast cells, and/or have direct effects on brain inflammation and ASD.

Retrospective analysis of aeroallergen's sensitization patterns in Edmonton, Canada.

BACKGROUND: Sensitization to common environmental aeroallergens plays a significant role in the pathogenesis and severity of respiratory allergic disorders, specifically asthma and allergic rhinitis. Understanding sensitization patterns helps clinicians tailor care more effectively. This study examines patterns of sensitization to aeroallergens in subjects suspected of having an allergic disease in Edmonton and catchment area. METHODS: Retrospective chart review of skin prick test (SPT) results to 11 environmental aeroallergens performed between January 1st and June 30th 2014 at a University-based clinic, where patients are referred for SPT by allergists, respirologists, otolaryngologists, internists and general practitioners. Potential differences in aeroallergen sensitization patterns were evaluated. RESULTS: A total of 623 patients (36.9% males; 63.1% females), aged 4-84 years (mean age 38.6 years) had SPT done, of which 438 (70.3%) had a positive test for at least one aeroallergen (atopy). There were no significant sex differences in the frequency of atopy (males: 71.3% versus females: 69.7%; p = 0.373). The frequency of sensitivity to particular allergens among atopic subjects was: cat (53.1%), house dust mites (50.3%), grass (39.2%), birch (23.7%), alternaria (23.7%), dog (17.3%), poplar (12.1%), cedar (9.6%), aspergillus (9.6%), hormodendrum (8%), and penicillium (6.2%). Of 438 atopic patients, 110 (25.1%) were mono sensitized, 199 (45.4%) oligosensitized (2-3 allergens), and 129 (29.5%) polysensitized (≥ 4 allergens). There were no significant differences between males and females in the odds of being oligo-sensitized (OR: 0.95; 95% CI 0.58, 1.57). Polysensitization was significantly more frequent in males 37.2% than in females 24.8%; (OR: 0.95; 95% CI 0.58, 1.57). CONCLUSION: Cat is the most frequent perennial allergen and timothy grass pollen the most frequent seasonal allergen in Edmonton and catchment area. There was no significant difference in the frequency of atopy between males and females. However, males were more likely to be polysensitized compared to females.

Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody results in adults with suspected food allergy.

BACKGROUND: Food allergy is a common clinical problem in adults. Given logistical barriers to conducting food challenges, the use of skin prick test (SPT) and specific IgE (sIgE) are important in establishing the diagnosis. The purpose of this study is to investigate the agreement of SPT and sIgE results in adults presenting to an allergy clinic with suspected food allergy. METHODS: Retrospective analysis of medical records at the University of Alberta Allergy Clinic between September 2013 and May 2015 was performed. Demographic, medical history as well as SPT and specific IgE results were recorded. Agreement of SPT and sIgE for individual food allergens was analyzed by Kappa statistics. RESULTS: Data from 260 patients was collected. The population was predominantly female, often having other atopic diseases. Very few food challenges were performed; IgE mediated food allergy was diagnosed in a minority (29.6 %) of cases. Kappa values which reached statistical significance were moderate for peanut ĸ = 0.535 (p = 0.0002, CI 0.364-0.707), walnut ĸ = 0.408 (p = 0.001 CI 0.159-0.657), pecan ĸ = 0.530 (p = 0.001 CI 0.211-0.848), and lobster ĸ = 0.543 (p = 0.004 CI 0.197-0.889), substantial for pistachio ĸ = 0.657 (p = 0.023 CI 0.224-1.000), codfish ĸ = 0.770 (p = 0.0002 CI 0.558-0.983), shrimp ĸ = 0.627 (p = 0.0006 CI 0.383-0.871) and egg white ĸ = 0.625 (p = 0.002 CI 0.293-0.957), almost perfect for cashew ĸ = 0.894 (p = 0.0008 CI 0.693-1.000) and salmon ĸ = 0.874 (p = 0.004 CI 0.705-1.000). CONCLUSIONS: The agreement between SPT and sIgE results on adults being evaluated for food allergy is at least moderate or better for peanut, walnut, pecan, pistachio, cashew, lobster, shrimp, codfish, salmon and egg white. This should be reassuring for patients who have contraindications or restricted access to either test as the results for the above allergens will likely agree. These findings may suggest that these tests could possibly be interchangeable in adults being evaluated for suspected food allergy and will aid primary care physicians in the triage of patients requiring allergist care.

Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study.

PURPOSE: To evaluate allergy skin testing as a diagnostic tool of adverse reactions to fluorescein and whether allergy and previous sodium fluorescein angiography (SFA) act as predisposing factors. METHODS: Patients with adequate indication for fluorescein angiography and normal skin responsiveness were subjected to allergy skin-prick and intradermal tests for fluorescein, followed by SFA. During SFA, adverse reactions were monitored and classified as mild, moderate or severe. Previous SFAs and adverse reactions as well as the presence of atopy were also registered. RESULTS: One thousand and thirty-seven patients were enrolled in the study and 1284 SFAs were executed. Forty-four patients (4.3%) developed 55 adverse reactions; among them 50 (3.8%) were mild, three (0.2%) moderate and two (0.16%) severe. None of the reactors produced positive skin tests to fluorescein. Patients with atopy and previous SFAs were not more susceptible to adverse reactions. CONCLUSION: The vast majority of adverse reactions to fluorescein are mild and not attributed to immunological mechanisms. Allergy skin tests cannot predict non-immunological reactions but their utility remains substantial in predicting anaphylaxis during SFAs and must be performed in patients reporting risk factors in their past medical history.