The Role of Lipids in Allergic Sensitization: A Systematic Review

Abstract

Background: Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults worldwide. The mechanisms underpinning the first phase of IgE-mediated allergy, allergic sensitization, are still not clear. Recently, the potential involvement of lipids in allergic sensitization has been proposed, with reports that they can bind allergenic proteins and act on immune cells to skew to a T helper type 2 (Th2) response.Objectives: The objective of this systematic review is to determine if there is strong evidence for the role of lipids in allergic sensitization.Methods: Nineteen studies were reviewed, ten of which were relevant to lipids in allergic sensitization to food allergens, nine relevant to lipids in aeroallergen sensitization.Results: The results provide strong evidence for the role of lipids in allergies. Intrinsic lipids from allergen sources can interact with allergenic proteins to predominantly enhance but also inhibit allergic sensitization through various mechanisms. Proposed mechanisms included reducing the gastrointestinal degradation of allergenic proteins by altering protein structure, reducing dendritic cell (DC) uptake of allergenic proteins to reduce immune tolerance, regulating Th2 cytokines, activating invariant natural killer T (iNKT) cells through CD1d presentation, and directly acting upon toll-like receptors (TLRs), epithelial cells, keratinocytes, and DCs.Conclusion: The current literature suggests intrinsic lipids are key influencers of allergic sensitization. Further research utilising human relevant in vitro models and clinical studies are needed to give a reliable account of the role of lipids in allergic sensitization.

Identification of Alpha-Gal conjugated Lipids in Saliva of Lone-Star Tick (Amblyomma americanum)

“…This highlights the importance of both inherent factors in ticks and those linked to the host in this complex process, as noted by Sharma et al (2021;2024). A recently proposed hypothesis suggests that the initiation of AGS (Alpha-Gal Syndrome) development is associated with α-gal conjugated lipids, as outlined by studies conducted by Roman-Carrasco et al ( 2021), Hopkins et al (2022), andChakrapani et al (2022).…”

“…While the role of N-glycan alpha-gal antigens in ticks and the contribution of tick bites to AGS induction have been well-established (Crispell et al, 2019; Sharma et al, 2024), a critical aspect concerning the involvement of lipid-bound alpha-gal in AGS induction remains to be investigated. Recent scientific reports have suggested lipid antigens may be crucial in allergic sensitization (Roman-Carrasco et al, 2021; Iweala et al, 2021, Hopkins et al, 2022). However, a fundamental knowledge gap exists regarding whether ticks possess α-gal bound lipid antigens in their saliva or salivary glands and whether these antigens can sensitize the host.…”

Peanut lipids influence the response of bronchial epithelial cells to the peanut allergens Ara h 1 and Ara h 2 by decreasing barrier permeability

“…How peanut allergens interact with airway epithelial cells and how this might affect the sensitization process is currently unknown. Moreover, increasing evidence points toward a role for lipids from the allergen source in the allergic sensitization process ( Bublin et al, 2014 ; Del Moral and Martínez-Naves, 2017 ; Hopkins et al, 2022 ). Our group previously showed that peanut lipids induced a pro-inflammatory response in human keratinocytes ( Palladino et al, 2018 ), which could provide Ara h 1 and Ara h 2 with the right milieu for the orchestration of Th2 immune responses leading to sensitization.…”

Invariant NKT cells are more abundant in peanut-allergic adults and a subset of CD8+ iNKT cells are depleted after peanut oil exposure

“…Previous research has shown peanut-derived lipids can interact with peanut allergens to promote a Th2-type allergic response (7,8). There are several hypothetical mechanisms for the role of allergen source-derived lipids in allergy (9), one of which is the ability of dendritic cells (DCs) to present lipids via CD1d molecules (10) to invariant natural killer T (iNKT) cells and subsequently activate iNKT cells to release Th2 cytokines.…”

“…In mice, they constitute approximately 1% of lymphocytes (13), thus making them an easy model for iNKT cell study, but the relevance of mice models to human disease is disputed. It is, thus, not surprising that there is limited existing research in this area utilizing human cellbased systems (9). This paper describes the development and application of a human in vitro co-culture system to study the role of peanut lipids and iNKT cells in a model of allergic sensitization.…”