Diagnosis and treatment of food allergies using a molecular approach

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Mar 15 2023

Food allergies involve adverse immunological reactions initiated by usually harmless proteins in food substances. Therefore, molecular assessments of food allergens with protein allergenicity assessments are essential to improve the diagnosis and prognosis of food allergies, as well as develop safe, effective, and long-term therapies.

Study: Molecular Approaches for Food Protein Allergenicity Assessment and the Diagnosis and Treatment of Food Allergies. Image Credit: Antonina Vlasova / Shutterstock.com

About the review

In a recent review published in the journal Foods, researchers discuss molecular methods for food allergy assessments, including diagnostic and prognostic markers, as well as existing therapies.

Herein, researchers elucidate pathophysiological mechanisms of food allergies, including identifying diagnostic and prognostic biomarkers and their use as potential therapeutical targets.

The pathophysiology of food allergies

Most food allergies are related to eggs, milk, tree nuts, peanut, wheat, soy, shellfish, and fish consumption and often arise due to immunological responses mediated by immunoglobulin E (IgE). IgE-mediated reactions involve antigen-presenting cell capturing, processing, and presenting of ingested food proteins (FPs) to helper T (Th) lymphocytes.

Th lymphocytes differentiate into Th2 lymphocytes and stimulate plasma cells derived from B lymphocytes to generate anti-allergen IgE. This form of IgE binds to high-affinity FcεRI IgE receptors present in basophils and mast cells.

Subsequent exposure to the allergen induces IgE crosslinking and cellular degranulation, thereby resulting in anaphylaxis-like symptoms among sensitized individuals. Th2-regulated responses to FPs have been observed in several gastrointestinal (GI) disorders, such as FP-induced allergic proctocolitis (FPIAP), eosinophilic esophagitis (EoE), FP-induced enterocolitis syndrome (FPIES), and FP-induced enteropathy (FPE).

Incorporating substances such as stabilizers, thickening agents, and emulsifiers in food substances could also trigger a food allergy. For example, pectin, widely used for gelling and can be obtained from lemons, apples, and peaches, has been associated with anaphylaxis among patients with allergies to non-specific lipid-transfer proteins (nsLTPs).

Flavonoids are bound to Mal d 1 by polar and hydrophobic interactions. Comparatively, glutathione-Mal d 1 binding occurs by van der Waal interactions and hydrophilic hydrogen binding, thus indicating differential alteration of Mal d 1 allergenicity.

In addition to modifying FP allergenicity, processing foods can alter digestibility. For example, FPs subjected to heat subsequently exhibit structural alterations that lead to their altered digestibility, which can ultimately impact biological interactions with immunological and epithelial cells.

Raw-type ovalbumin (Gal d II) digestion promotes pro-inflammatory (IL-6) and pro-allergenic (thymic stromal lymphopoietin) expression among human colorectal adenocarcinoma (Caco-2) cell lines. Conversely, the digestion of heat-treated allergens reduces the cytokine expression, thus indicating that heat treatment may decrease ovalbumin protein-associated allergenic epitope release.

Molecular markers for diagnosis and treatment of food allergies

Previous studies have reported that anaphylaxis severity is related to greater anti-Cor a-11, 14 IgE titers and that component-resolved diagnosis (CRD) systems aid in identifying high-risk individuals. A notable correlation has been observed between the 2S structural characteristics, FP allergenicity, and cross-reactivity.

An increase in the number of tick bites increases the likelihood of a class switch from anti-α-Gal IgG antibodies to IgE antibodies. Thus, serological α-Gal IgG titers could be used as prognostic markers of meat allergies.

Oyster tropomyosin protein (Cra g 1)  has been identified as a key allergen detected by anti-tropomyosin Cra g 1 IgE antibodies, and cross-reactivity between tropomyosin obtained from dust mites and prawns, likely based on conserved IgE-binding epitope existence. As a result, recombinant oyster tropomyosin proteins can be utilized to develop CRD diagnostics and immunological therapies.

Oral food challenge (OFC) using allergens is considered the gold standard for diagnosing food allergies. However, due to the limitations and risks associated with this approach, other IgE-based evaluations, including basophil activation tests and skin prick tests, are used for less invasive and safer diagnoses. Nevertheless, easy access to oral mucosal sites could facilitate food allergy diagnosis and improve the understanding of disease progression in complex allergy syndromes.

Oral mucosal assessments may aid in depicting immunological diseases and evaluating therapeutic efficacy to develop novel treatment options. Among individuals with food allergies mediated by IgE, avoiding the triggering allergen has provided therapeutic benefits over the years.

Treatment strategies currently under evaluation include allergen-targeted immunotherapies (IT) using different delivery routes, as well as novel approaches using nanoparticles, hypoallergenic substances, microbiome balance-restoring substances, and biologics.

Allergen-targeted immunotherapies involve administering specific quantities of food allergens to patients to induce tolerance and are considered reliable therapeutic options. In addition to hypoallergenic and immunological therapies, probiotics/prebiotics/synbiotics, as well as monoclonal antibodies, have demonstrated therapeutic effects for food allergies. However, further research, including clinical trials, is needed to enable diagnosing and treating food allergies with novel therapies.

Conclusions

Overall, the review findings highlight the pathophysiological mechanisms of food allergies and diagnostic, prognostic, and therapeutic options to improve the standard of care of affected individuals.