The journal of allergy and clinical immunology. In practice •
The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.
Jappe U, Minge S, Kreft B, Ludwig A, Przybilla B, et al.
Allergy •
Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-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 α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. Three serum groups, α-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 α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. Singleplex allergy diagnostics using the α-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 α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-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.
Maurer M, Church MK, Metz M, Starkhammar M, Hamsten C, et al.
International archives of allergy and immunology •
Tick bite-induced galactose-α-1,3-galactose (α-Gal) IgE and subsequent ingestion of red meat may cause delayed severe allergic reactions including urticaria, gastrointestinal symptoms or anaphylaxis. We tested the hypothesis that increased levels of IgE to α-Gal due to tick bites and the subsequent ingestion of red meat or meat products may possibly be an un(der)recognized cause of chronic spontaneous urticaria (CSU). Levels of IgE to α-Gal and total IgE were measured (ImmunoCAP, Phadia AB/Thermo Fisher Scientific) in 83 patients (61 female and 22 male, median age 43 years, range 18-82) from the Department of Dermatology and Allergy, Charité - Universitätsmedizin, Berlin, Germany. All had been clinically diagnosed with moderate-to-severe CSU of a median duration of 2.9 years (range 0.1-50). Eighty of the 83 patients (96%) had undetectable (<0.1 kUA/l) serum levels of IgE against α-Gal. The levels in the remaining 3 were all low (0.25, 0.4 and 3.1 kUA/l). In no patient, including those with measurable serum levels of IgE against α-Gal, was eating red meat associated with the development of symptoms of urticaria. Our results indicate that an allergic response to α-Gal is highly unlikely to be a hitherto unrecognized common cause of CSU.
