Abundance and Stability as Common Properties of Allergens

Abstract

There have been many attempts to identify common biophysical properties which differentiate allergens from their non-immunogenic counterparts. This review will focus on recent studies which examine two such factors: abundance and stability. Anecdotal accounts have speculated that the elevated abundance of potential allergens would increase the likelihood of human exposure and thus the probability of sensitization. Similarly, the stability of potential allergens dictates its ability to remain a viable immunogen during the transfer from the source to humans. This stability could also increase the resilience of potential allergens to both gastric and endosomal degradation, further skewing the immune system toward allergy. Statistical analyses confirm both abundance and stability as common properties of allergens, while epidemiological surveys show a correlation between exposure levels (abundance) and allergic disease. Additional studies show that changes in protein stability can predictably alter gastric/endosomal processing and immunogenicity, providing a mechanistic link between stability and allergenicity. However, notable exceptions exist to both hypotheses which highlight the multifaceted nature of immunological sensitization, and further inform our understanding of some of these other factors and their contribution to allergic disease.

Scientific Opinion on development needs for the allergenicity and protein safety assessment of food and feed products derived from biotechnology

“…Interestingly, recent studies reported differences in biophysical properties and structural dynamics between shrimp and pig tropomyosins, despite their high degree of conservation, which may explain differences in their allergenic potential (James et al, 2018 ; James and Nanda, 2020 ). Finally, although abundance might not be a universal characteristic of all food allergens, it seems to be a predisposing factor that enhances their chance to interact with the immune system, when coupled with other biochemical characteristics, that could produce a food allergen (Bannon, 2004 ; Foo and Mueller, 2021 ).…”

“…Nevertheless, there are possibly a few distinct biochemical characteristics associated with the different protein families that mainly correlate to the elicitation capacity of certain allergens. These characteristics are determined by the 3D structure of proteins, which confer the physicochemical and biological properties governing protein stability, such as the capacity to bind ligands (ranging from metal ions to lipids) and/or resistance to protease degradation and thermal stability (Radauer et al, 2008 ; EFSA GMO Panel, 2017 , 2021 ; Foo and Mueller, 2021 ). Ligands generally increase the stability of allergens to thermal and/or proteolytic degradation (Moreno et al, 2005 ; Vassilopoulou et al, 2006 ; Bossios et al, 2011 ; Berecz et al, 2013 ; Petersen et al, 2014 ) and can also act as immunomodulatory agents that favour Th2 polarisation.…”

“…Possible links between the proteins’ biological function/activity and their allergenicity are emerging (Ozias‐Akins & Breiteneder, 2019 ; Foo and Mueller, 2021 ). For example, the proteolytic activity of some food allergens might contribute to the sensitisation process via different mechanisms such as the cleavage of certain proteinase‐activated receptors leading to the release of pro‐inflammatory cytokines (Cayrol et al, 2018 ; Scott et al, 2018 ; Dietz et al, 2019 ) or through the direct proteolysis of tight junctions, and other extracellular structures enhancing the intestinal epithelial barrier permeability (Grozdanovic et al, 2016 ).…”

“…To be recognised as an allergen, exogenous antigens must first be internalised into the endosome of APC and then are subjected to endosomal degradation, where they are exposed to cathepsin proteases under increasingly acidic and reducing conditions. The resulting peptide fragments are loaded onto the class two major histocompatibility complex (MHCII) and presented on the cell surface for recognition by T‐cell receptors (Foo and Mueller, 2021 ). Moreover, the intestinal barrier has a crucial role in protecting the organism against pathogens and possibly harmful substances derived from the external environment (Cardoso‐Silva et al, 2019 ).…”

Detection of Allergenic Proteins in Foodstuffs: Advantages of the Innovative Multiplex Allergen Microarray-Based Immunoassay Compared to Conventional Methods

“…In particular, food processing often leads to a decrease in allergenicity [ 9 , 10 , 11 , 12 ], although no change, or even an increase, have also been reported for foods such as fish [ 13 ] and peanut [ 14 , 15 ]. Therefore, the combination of different factors and different types of processing methods can be exploited to obtain foods with lower allergenicity having a lower sensitizing power [ 16 ], which can also be consumed by some specific sub-populations of allergic patients. In fact, an increasing number of studies are currently in progress to test the effectiveness of several classic and emerging processing methods in the reduction of the allergenicity of specific foods [ 17 , 18 ].…”