Peanut lipids display potential adjuvanticity by triggering a pro‐inflammatory response in human keratinocytes

Palladino, Chiara; Narzt, Marie-Sophie; Bublin, Merima; Schreiner, Maximilian; Humeniuk, Piotr; Gschwandtner, Maria; Häfner, Christine; Hemmer, Wolfgang; Hoffmann‐Sommergruber, Karin; Mildner, Michael; Palomares, Óscar; Грубер, Флориан; Breiteneder, Heimo

doi:10.1111/all.13475

Cited by 24 publications

(44 citation statements)

References 12 publications

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“…Natural Ara h 2 (nAra h 2) was purified from roasted peanuts, as previously described. 25 Reduction, alkylation, and physicochemical characterization of recombinant and natural proteins nAra h 2, wtAra h 2, and mtAra h 2 underwent reduction and alkylation to destroy conformational IgE epitopes. All native and red/alk proteins were subjected to detailed characterization with respect to their identity, secondary structure, and aggregation.…”

Section: Preparation Of Pe and Natural Ara Hmentioning

confidence: 99%

Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

Tscheppe

Palmberger

Rijt

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: To date, no safe allergen-specific immunotherapy for patients with peanut allergy is available. Previous trials were associated with severe side effects. Objective: We sought to determine the relative importance of conformational and linear IgE-binding epitopes of the major peanut allergen Ara h 2 and to produce a hypoallergenic variant with abolished anaphylactogenic activity. Methods: Wild-type Ara h 2 and a mutant lacking the loops containing linear IgE epitopes were produced in insect cells. Conformational IgE epitopes were removed by unfolding these From a

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Section: Preparation Of Pe and Natural Ara Hmentioning

confidence: 99%

Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

Tscheppe

Palmberger

Rijt

et al. 2020

Journal of Allergy and Clinical Immunology

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“…In human primary keratinocytes, lipids from peanut have been implicated in enhancing the allergenicity of allergens by inducing an inflammatory response and inhibiting IL-10 production to facilitate allergen transfer and possibly sensitization. 13 The involvement of IL-33, TSLP, and IL-25, often referred to as "alarmins" in the sensitization process, in the maintenance of allergic responses and exacerbation of food allergy, asthma, and atopic dermatitis is well recognized. [14][15][16] Epithelial cells serve as a source of these mediators, which are potent upstream elements of the allergic responses and have become targets to treat and facilitate food allergy.…”

Section: Food Allergy and Barrier Functionmentioning

confidence: 99%

“…As suppression of these mechanisms resulted in the abrogation of food‐induced allergic responses, these exciting data may add to knowledge of the benefit of blocking IL‐13/IL‐4 pathways. In human primary keratinocytes, lipids from peanut have been implicated in enhancing the allergenicity of allergens by inducing an inflammatory response and inhibiting IL‐10 production to facilitate allergen transfer and possibly sensitization …”

Section: Introductionmentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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“…Here, lipid extracts from nuts favor allergen-induced inflammatory responses by increasing IL-4/IL-10 ratios and IL-1β secretion from human monocyte-derived DCs (moDCs) ( 11 ). Moreover, purified peanut-derived lipids applied together with either Arh 1 or Ara h 2 were reported to trigger pro-inflammatory responses (IL-8, IL-6, and TNF-α secretion) while inhibiting anti-inflammatory IL-10 release from human keratinocytes ( 12 ).…”

Section: Impact Of Lipids On the Sensitization Capacity Of Food Allermentioning

confidence: 99%

Interaction of Non-Specific Lipid-Transfer Proteins With Plant-Derived Lipids and Its Impact on Allergic Sensitization

Scheurer

Schülke

2018

Front. Immunol.

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Non-specific lipid-transfer proteins (nsLTPs) represent a family of ubiquitous plant proteins belonging to the prolamin superfamily. nsLTPs are characterized by a globular α-helical structure stabilized by four disulfide bonds and a hydrophobic cavity which acts as ligand-binding site for a broad spectrum of lipids and hydrophobic molecules. nsLTPs are involved in membrane biogenesis and in the adaption of plants to abiotic and biotic stress. They display antimicrobial activity by the ability to permeabilize the cell membrane of phytopathogens. Moreover, in the presence of lipids, nsLTPs are suggested to activate the plant immune system by a receptor-dependent mechanism. Additionally, nsLTPs from pollen and plant-derived food, in particular type 1 nsLTPs (9 kDa), are described as potent allergens. Within the nsLTP family Pru p 3 from peach is the clinically most relevant allergen which can cause genuine food allergy and frequently elicits severe clinical reactions. So far, the allergenic properties of nsLTPs are attributed to both their low molecular mass and their high thermal and proteolytic stability which allow them to reach the immune system in a biological intact form. Recently, the interaction of nsLTPs with lipids has been suggested to increase their allergenic properties and to promote the allergic sensitization to these proteins. This review will summarize the current knowledge on diversity of lipid ligands of plant LTPs, and illustrate recent studies performed with allergenic nsLTPs to investigate the effect of lipid binding on the structural modification and IgE-binding properties of proteins, and finally the potential effect on the innate immune responses.

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Peanut lipids display potential adjuvanticity by triggering a pro‐inflammatory response in human keratinocytes

Cited by 24 publications

References 12 publications

Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

Recent developments and highlights in food allergy

Interaction of Non-Specific Lipid-Transfer Proteins With Plant-Derived Lipids and Its Impact on Allergic Sensitization

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