A comprehensive review of food allergy (FA)-related studies published between 2021 and 2023 is currently in press with the Journal of Allergy and Clinical Immunology. This text highlights the increasing burden of FA within the developing world, gradual stabilization in Europe and other developed regions, and promising research into the mechanisms that cause FA and its diagnosis and treatment.

Study: Feast for Thought: A Comprehensive Review of Food Allergy 2021-2023. Image Credit: Yavdat / Shutterstock

Environmental aspects, genetics, and prevalence of FA

The incidence of FA has historically been more common in urban areas and developed nations, with one estimate suggesting that the pooled lifetime prevalence is as high as 19.9% in Europe. Nonspecific lipid transfer proteins (nSLTP) are probably the most common explanation for FA in Southern Europe and have gotten more widespread across the remainder of Europe, Latin America, China, and Japan.

Environmental changes and ethnicity can have a joint role in the event of FA, as indicated by an estimated FA prevalence of 15% amongst Australian children with Asian heritage compared with 1.1% for those with Singaporean heritage. Studies on the role of genetics have identified human leukocyte antigens (HLAs) which might be related to certain FAs, akin to single nucleotide polymorphism (SNP) rs9277630 and HLA-DPB1*02:01:02 for wheat allergies.

Hospital admissions for FA-related anaphylaxis have risen sharply over time, with this response disproportionately affecting teenage and younger children. While the variety of fatalities has remained stable, nuts and cow milk allergies are the leading explanation for death from FA-induced anaphylaxis.

Mouse and human in-vitro studies examine FA mechanisms

A mouse study found that individuals who got peanut butter while also exposed to peanuts of their environment were less more likely to turn into sensitive and allergic, which might be mediated by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and induction of T-regulatory cells. Other studies indicated that damage to the gut epithelial barrier (akin to by dishwater detergents) could cause FA.

Loss-of-function mutations throughout the filaggrin gene are actually regarded as related to the persistence of egg and cow’s milk allergies. Alpha-gal, which is present in glycolipids and glycoproteins, may contribute to peanut allergies. Nevertheless, Ara h 2 is the dominant peanut allergen and should form complexes with Ara h 1 and Ara h 3, resulting in cross-reactivity and a biased estimation of the immunological importance of the latter two.

An interesting study on peanut-allergic patients found distinct biomarkers in patients with lower thresholds of peanut tolerance, akin to higher peanut-specific immunoglobulin E (IgE) levels and peanut-specific IgE/IgG4 ratios. A lower reactivity threshold was related to the presence of peanut-specific Th2 cells, which were successfully eliminated by oral immunotherapy. Other studies showed that clinical phenotypes interact with allergen-specific IgE traits, that are then reflected in basophil responses.

Highlights on the topics of the novel publications about mechanisms of food allergy and tolerance mentioned within the text. Figure built with Biorender.

Developments in FA diagnosis and clinical guidelines

The gold standard for the definitive diagnosis of FA is taken into account to be the oral food challenge (OFC), which is dear, time-consuming, and may result in severe allergic reactions. Nevertheless, guidelines with less rigid challenge stop criteria and more subjective symptoms may lead to the overestimation of FA without reducing rates of anaphylaxis.

Recent systematic reviews and meta-analyses have highlighted functional specificity and sensitivity cut-offs to guide allergy test result interpretation. Extensive population-based longitudinal studies are required to raised understand risk aspects for FA severity, but recent scoring systems akin to the Food Allergy Severity Rating (FASS) and the Definition of Food Allergy Severity (DEFASE) are essential developments.

The basophil activation test (BAT) is a promising recent test that has been integrated into clinical practice. The BAT is a flow cytometry-based test involving all components of the response, including serum IgE (sIgE), effector cells, and other antibodies. It has emerged as the very best predictor of allergic response thresholds and severity to baked eggs when it comes to accuracy, specificity, and sensitivity while also demonstrating high reliability and reproducibility across multiple laboratories. While other tests, akin to peptide-specific IgE, even have potential, they require further validation and research.

Recent therapies, drugs, and vaccines

Ongoing research highlights the role of newer therapies, medicines, and vaccines in tackling FA. For instance, oral immunotherapy (OIT) has been shown to extend desensitization, sustained unresponsiveness, and even consumption of milk and peanuts for preschool-aged children. Nevertheless, further research is required to find out its long-term effects.

Similarly, epicutaneous immunotherapy (EPIT) has been established as well-tolerated and secure for youngsters with peanut allergies but has also not been studied in the long run. Sublingual immunotherapy (SLIT) is being tested together with OIT to treat cow’s milk allergies, while oral mucosal immunotherapy (OMIT) may allow the delivery of upper doses of allergens.

Amongst drugs being tested to scale back the severity of allergies, omalizumab appears to scale back reactions and improve the standard of life for individuals with allergies while also increasing the dose of allergens they’ll tolerate. Higher doses of omalizumab are simpler without an associated increase in opposed effects.

Other medications currently being tested include ligelizumab, abrocitinib, abatacept, and remibrutinib. Since gut microbial diversity, composition, and metabolic activity are related to food tolerance and allergy, probiotics are also being studied for FA relief and look like more helpful for cow’s milk allergies than peanut allergies. Fusion and mRNA vaccines are also in development.

Emerging evidence: Is it possible to stop food allergies?

Studies have explored the links between dietary diversity while pregnant and the primary 12 months of life, with results indicating that yogurt and vegetables reduce the incidence of allergic disease but not FA.

An ongoing trial focuses on whether consuming allergenic food items while pregnant could reduce the offspring’s risk of developing FA. At the identical time, one other study is investigating whether probiotics could reduce egg, wheat, soya, and cow’s milk allergy-related symptoms in month-old infants.

Skin interventions akin to emollients have been evaluated, with concerning findings that they’ll increase FA risk and never prevent it. The early introduction of peanuts to infant diets has not been shown to scale back peanut allergy prevalence, based on a trial in Australia.

Conclusions

Overall, this comprehensive evaluation of recent advances in FA-related research highlights the importance of emerging studies in improving the diagnosis and management of varied allergies and indicates avenues for further investigation. The outcomes of ongoing trials are eagerly awaited by the medical community and individuals living with food allergies and their families.