Project description:BackgroundAs extract-based skin testing as well as in vitro tests for major allergens have their own advantages, both procedures are usually performed in routine settings. In times of shortages in medical staff and supplies, we asked ourselves, how many patients would be underdiagnosed, if only one test could be used.MethodsIn a retrospective analysis, we investigated a cohort of 2646 patients seen by a single physician in a large Austrian outpatient allergy clinic in 2018. Only patients with an allergen source-specific history and pairs of extract-based skin prick (SPT) and in vitro molecular allergy tests to major allergens were included.ResultsFor all tested allergen sources, sensitivity was higher for SPT than for sIgE-based molecular allergy testing. Concerning 1006 birch pollen-allergic patients, 791 (78.6%) had positive results with both tests, while 153 (15.2%) only with the SPT and 62 (6.2%) only with the sIgE to Bet v1. The other allergen sources showed similar results: For house dust mite 816/1120 (72.9%), grass pollen 1077/1416 (76.1%) and cat 433/622 (69.6%) remained test-positive with both procedures, whereas in 276 (24.6%), 224 (15.8%) and 173 (27.8%) times only the SPT and 28 (2.5%), 115 (8.1%) and 16 (2.6%) times only the sIgE to Der p1/2/23, Phl p1/5 and Fel d1 showed a positive result. Each comparison was statistically significant (each p < 0.0001, Chi-squared test).ConclusionsScreening for allergy with major molecular allergens has lower sensitivity when compared with extract-based skin tests. A combination of both is required for an optimal sensitivity.
Project description:Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined ?-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced ?-cell secretory capacity and ?-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.
Project description:BACKGROUND:Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-?-(1,3)-galactose (?-Gal). It is known that ?-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. ?-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different ?-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against ?-Gal. METHODS:Three serum groups, ?-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for ?-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated ?-Gal. RESULTS:Singleplex allergy diagnostics using the ?-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against ?-Gal reveals individual IgE sensitization profiles for ?-Gal-containing analytes. An ?-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-?-Gal) was identified, which is associated with MA. CONCLUSIONS:Detection of individual sensitization patterns with different ?-Gal-containing analytes provides the basis for an individual allergy diagnosis for ?-Gal-sensitized patients. Higher amounts of ?-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.
Project description:Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant natural antibody in humans, comprising about 1% of immunoglobulins and is also naturally produced in apes and Old World monkeys. The anti-Gal ligand is a carbohydrate antigen called "α-gal epitopes" with the structure Galα1-3Galβ1-4GlcNAc-R. These epitopes are expressed as major carbohydrate antigens in non-primate mammals, prosimians, and New World monkeys. Anti-Gal is exploited in cancer vaccines to increase the immunogenicity of antigen-presenting cells (APCs). Cancer cells or PDAC tumor lysates are processed to express α-gal epitopes. Vaccination with these components results in in vivo opsonization by anti-Gal IgG in PDAC patients. The Fc portion of the vaccine-bound anti-Gal interacts with Fcγ receptors of APCs, inducing uptake of the vaccine components, transport of the vaccine tumor membranes to draining lymph nodes, and processing and presentation of tumor-associated antigens (TAAs). Cancer vaccines expressing α-gal epitopes elicit strong antibody production against multiple TAAs contained in PDAC cells and induce activation of multiple tumor-specific T cells. Here, we review new areas of clinical importance related to the α-gal epitope/anti-Gal antibody reaction and the advantages in immunotherapy against PDAC.
Project description:Alpha-gal (AG) allergy is an IgE-mediated allergic reaction to galactose-alpha-1,3-galactose found in mammalian meat. Heparin, being derived from porcine intestinal tissue, may have a degree of cross-reactivity with AG antigen and thus place patients at risk for allergic and even anaphylactic reactions. This is especially important in patients with myocardial infarction (MI) and mechanical circulatory support, such as a left ventricular assist device (LVAD), since anticoagulation is immediately required. Therefore, individualized assessment and preoperative planning is needed regarding the use of heparin vs. nonheparinoid products in such a population.
Project description:Documented penicillin allergies have been associated with an increased risk of adverse outcomes. The goal of this project was to assess the effectiveness and feasibility of a pharmacist-led penicillin allergy "de-labeling" process that does not involve labor-intensive skin testing or direct oral challenges. Adult patients with penicillin allergies were identified and interviewed by an infectious diseases pharmacy resident during a 3-month pilot period. Using an evidence-based standardized checklist, the pharmacist determined if an allergy qualified for de-labeling. In total, 66 patients were interviewed during the pilot period. The average time spent was 5.2 min per patient interviewed. Twelve patients (18%) met the criteria for de-labeling and consented to the removal of the allergy. Four patients (6%) met the criteria but declined removal of the allergy. In brief, 58.3% of patients (7/12) who were de-labeled and 50% of patients (2/4) who declined de-labeling but had their allergy updated to reflect intolerance were subsequently prescribed beta-lactam antibiotics and all (9/9, 100%) were able to tolerate these agents. A pharmacist-led penicillin allergy de-labeling process utilizing a standardized checklist is an effective and feasible method for removing penicillin allergies in patients without a true allergy.
Project description:BackgroundPrevious studies have predominately examined associations of respiratory allergy and skin allergy with ADHD, but little is known about the association between food allergy and ADHD.MethodsWe included 192,573 children aged 4-17 years from the National Health Interview Survey (NHIS), a leading health survey in a nationally representative sample of the US population. Allergy conditions and ADHD were defined based on an affirmative response in the NHIS questionnaire. We used weighted logistic regression to estimate the odds ratio (OR) of ADHD.ResultsAmong the 192,573 children, 15,376 reported ADHD diagnosis. The prevalence of ADHD was higher among children with allergic conditions: 12.66% vs. 7.99% among children with and without food allergy; 12.16% vs. 7.63% among children with and without respiratory allergy; and 11.46% vs. 7.83% among children with and without skin allergy. After adjusting for covariates, the OR of ADHD was 1.72 (95% CI, 1.55-1.91) comparing children with and without food allergy, 1.50 (95% CI, 1.41-1.59) comparing children with and without respiratory allergy, and 1.65 (95% CI, 1.55-1.75) comparing children with and without skin allergy. The observed associations remained significant after mutual adjustment for other allergic conditions.ConclusionsIn a nationally representative sample of US children, we found a significant association of common allergic conditions (food allergy, respiratory allergy, and skin allergy) with ADHD.