Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:To critically appraise the recent most relevant studies in the rapidly advancing field of food oral and sublingual immunotherapy. RECENT FINDINGS/RESULTS:Food allergen-specific immunotherapy via oral (OIT) and sublingual route (SLIT) increases the threshold of reactivity to peanut, cow's milk, egg, wheat, and many other foods in the majority of the treated individuals. This desensitized state is contingent upon the continued ingestion of the maintenance doses of the food. Permanent oral tolerance is achievable in a smaller subset of the treated individuals. The optimal duration of therapy has not been firmly established but is likely dependent on the phenotype (severity and persistence). Efficacy of food-OIT is superior compared with SLIT, whereas the safety of OIT is less favorable. Standardization of treatment protocols, maintenance dosing, duration of therapy, target populations and harmonization of the outcomes are top priorities at this stage. SUMMARY/CONCLUSIONS:OIT and SLIT represent two different routes of food allergen-specific immunotherapy. Although significant progress has been made in the last decade, both treatment modalities are still in the very early stages of development and further investigations are necessary to optimize the protocols and improve safety while maximizing efficacy.

Exopalaemon modestus (EM) is a shrimp delicacy that could cause food allergy, the major allergen of EM is Exo m 1. The amino acid (AA) sequence, IgE-binding epitopes and allergenic peptides in gastrointestinal (GI) digests of Exo m 1, and their effects on basophil function were investigated. Exo m 1 has an AA-sequence of high similarity with other shrimp tropomyosins, while not 100% matching. The IgE-binding epitopes of Exo m 1 are epitope 1 (43-59, VHNLQKRMQQLENDLDS), epitope 2 (85-105, VAALNRRIQLLEEDLERSEER), epitope 3 (131-164, ENRSLSDEERMDALENQLKEARFLAEEADRKYDE), epitope 4 (187-201, ESKIVELEEELRVVG) and epitope 5 (243-280, ERSVQKLQKEVDRLEDELVNEKEKYKSITDELDQTFSE). Among the thirty-three peptides of Exo m 1 identified in GI digests, two were highly recognized by IgE, twenty-four moderately or weakly bound IgE, and seven had no IgE-reactivities. These IgE-binding epitopes and GI digestion induced-allergenic peptides could activate basophil degranulation, and CD63 and CD203c expression, they could be potential peptide-based immunotherapy for shrimp allergic individuals.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that has been well-characterized clinically, yet it is still poorly understood. Acute FPIES is characterized by vomiting 1-4 h and/or diarrhea within 24 h after ingestion of a culprit food. Chronic FPIES is the result of chronic exposure to an offending food that can result in chronic watery diarrhea, intermittent vomiting, and failure to thrive. FPIES typically presents in infancy and self-resolves by school age in most patients. Adult-onset FPIES is rare, but it has been reported. Cow's milk and soy are the most common triggering foods in infants in the US, and as solids are introduced in the diet, FPIES reactions to grains (rice, oat) increase in prevalence. Variability in common trigger foods exists depending on the geographical origin-for example, fish is a frequent trigger in Spanish and Italian patients. Heavy reliance on a detailed history is required for the diagnosis as physical exam findings, laboratory tests, and/or imaging studies are suggestive and not specific for FPIES. Oral food challenges remain the gold standard for confirming diagnosis, and the challenge protocol may be for an individual depending on risk of reaction, prior reaction severity, and positive-specific IgE status. The recent development of diagnostic criteria in 2017 will serve to increase recognition of the disorder and allow for early implementation of management strategies. Acute management during reactions includes IV hydration, anti-emetics, and IV corticosteroids. Reaction prevention strategies include strict food avoidance until the physician deems a food reintroduction challenge clinically appropriate. Future efforts in FPIES research should be aimed at elucidating the underlying disease mechanisms and possible treatment targets.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate-severe reactions and as a first-line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects.

Tropomyosin (TM) is the main allergen of shrimp. Glycation reportedly reduced the allergenicity of TM, and the allergenicity reduction was heavily dependent upon the sources of saccharides. In this work we investigated, how glycation of tropomyosin by functional oligosaccharides affected the allergenicity. Compared to TM, the TM glycated by galacto-oligosaccharide (TM-GOS), mannan-oligosaccharide (TM-MOS) and maltopentaose (TM-MPS) had lower allergenicity and induced weaker mouse allergy responses. While the TM glycated by fructo-oligosaccharide (TM-FOS) had stronger allergenicity and induced severe mouse allergy symptoms, due to the generation of neoallergns that belonged to advanced glycation end products (e.g. CML). Therefore, GOS, MOS and MPS could be applied to desensitize shrimp TM-induced food allergy through glycation, while FOS was not suitable to reduce TM allergenicity. Glycation of TM by GOS, MOS and MPS, especially for MPS, significantly reduced allergenicity and alleviated allergy symptoms, which could be potentially explored for immunotherapy for shrimp-allergic patients.

BACKGROUND:We sought to determine whether an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) was tolerated by infants with cow's milk protein allergy (CMPA). METHODS:A whey-based EHF (Test formula) containing 2'fucosyl-lactose (2'FL) and lacto-N-neotetraose (LNnT) was assessed for clinical hypoallergenicity and safety. The Control formula was a currently marketed EHF without HMO. Children with CMPA, aged 2 months to 4 years, were assessed by double-blind, placebo-controlled food challenges (DBPCFC) to both formulas, in randomized order. If both DBPCFC were negative, subjects participated in a one-week, open food challenge (OFC) with the Test formula. Symptoms and adverse events were recorded. Hypoallergenicity was accepted if at least 90% (with 95% confidence intervals) of subjects tolerated the Test formula. RESULTS:61). There was one allergic reaction to the Test, and one to the Control formula. On the mITT analysis, 63 out of 64 (98.4%; 95% CI lower bound 92.8%), and on the PP analysis 60 out of 61 (98.4%; 95% CI lower bound 92.5%) participants tolerated the Test formula, confirming hypoallergenicity. CONCLUSION/CONCLUSIONS:The whey-based EHF supplemented with 2'FL and LNnT met the clinical hypoallergenicity criteria and can be recommended for the management of CMPA in infants and young children.