Unusual and Unexpected Allergic Reactions Can Be Unraveled by Molecular Allergy Diagnostics

Abstract

The fifth class of immunoglobulin, immunoglobulin E (IgE) was discovered in 1967 and has had immense importance for the understanding, diagnosis, and treatment of allergic disease. More than 50 years have passed and efforts to characterize, standardize, and refine allergens with the aim to improve clinical diagnosis and allergen-specific immunotherapy are still ongoing. Another important breakthrough was made in 1999 with the introduction of component-resolved diagnostics (CRD), making it possible to quantify IgE antibodies against individual allergen proteins for diagnostic purposes at a molecular level. The progress and developments made in allergy diagnosis often originate from clinical observations and case studies. Observant physicians and health-care personnel have reported their findings in the medical literature, which in turn has inspired researchers to become involved in clinical research. Allergists continuously encounter new allergies and are often asked by their patients how to prevent new reactions. In the current article, we focus on recent clinical observations that can now be explained by CRD. The examples taken concern allergic reactions toward peanuts, tree nuts, lemon kernels, health drinks, meat, insects, dog dander, cannabis, and semen. We now have an improved understanding of why patients may react in a serious or unexpected way, as illustrated by these examples, yet many other clinical observations remain unexplained. The aim of this review is to highlight the importance of clinical observations among allergic patients, focusing on systemic, or unusual and unexpected allergic reactions, where component-testing has further refined the diagnosis of IgE-mediated allergy.

Keywords: Allergen components; Cannabis allergy; Cashew allergy; Component-resolved diagnostics; Crocodile allergy; Dog allergy; Immunoglobulin E; Insect allergy; Peanut allergy; Red meat allergy; Soy allergy; Tree-nut allergy.

Fig. 1

Botanical relationship showing the relations between different species. This classification does not include all botanical classifications.

Fig. 2

Reprinted from [51] with permission. Comparison of chicken and crocodile α-parvalbumin. a Three-dimensional model of chicken parvalbumin, protein surface coloring by identity to crocodile parvalbumin. Red, identical residues; gray, variable residues. b Amino acid sequence alignment of chicken and crocodile parvalbumins as allergens involved in the clinical cross-reaction to both meats.

Fig. 3

Reprinted with permission from [67]. Sixty children (age, 10–18 years) sensitized to dog-dander extract underwent NPTs with dog-dander extract. Measurement of IgE levels to dog dander and Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kU_A/L or greater was considered positive. Results: there was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result. Sensitization to lipocalins (OR, 6.0; 95% CI, 1.04–34.5), in particular, Can f 4 (OR, 6.80; 95% CI 1.84–25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59–20.8) were associated with a positive NPT result. Mono-sensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01–33.0). IgE, immunoglobulin E; OR, odds ratio; NPT, nasal provocation test.