Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.

BACKGROUND AND OBJECTIVE: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping. METHODS: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens. RESULTS: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes. CONCLUSION: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Cross-reactivity to fish and chicken meat - a new clinical syndrome.

BACKGROUND: Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. METHODS: Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing. RESULTS: Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings. CONCLUSIONS: Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.

Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens.

BACKGROUND: The majority of fish-allergic patients are sensitized to parvalbumin, known to be the cause of important IgE cross-reactivity among fish species. Little is known about the importance of fish allergens other than parvalbumin. OBJECTIVE: The aim of this study was to characterize hitherto undefined fish allergens in three commonly consumed fish species, cod, salmon and tuna, and to evaluate their importance for in vitro IgE-diagnosis in addition to parvalbumin and fish gelatin. METHODS: Sixty-two patients were diagnosed by clinical history, skin prick tests and specific IgE to fish extracts. Two new fish allergens from cod, salmon and tuna were identified by microsequencing. These proteins were characterized by immunoblot, ELISA and mediator release assay. Purified parvalbumin, enolase, aldolase and fish gelatin were used for quantification of specific IgE in ELISA. RESULTS: Parvalbumin and two other allergens of 50 and 40 kDa were detected in IgE-immunoblots of cod, salmon and tuna extracts by most patient sera. The 50 and 40 kDa proteins were identified as beta-enolase and fructose-bisphosphate aldolase A respectively. Both purified enzymes showed allergenic activity in the mediator release assay. Indeed, 72.6% of the patients were sensitized to parvalbumin, 20% of these had specific IgE to salmon parvalbumin only. IgE to enolases were found in 62.9% (0.5-95.0 kUA /L), to aldolases in 50.0% (0.4-26.0 kUA /L) and to fish gelatin in 19.3% (0.4-20.0 kUA /L) of the patients. Inter-species cross-reactivity, even though limited, was found for enolases and aldolases by IgE-inhibition ELISA. CONCLUSIONS AND CLINICAL RELEVANCE: Fish enolase and aldolase have been identified as important new fish allergens. In fish allergy diagnosis, IgE to enolase and aldolase are especially relevant when IgE to parvalbumin are absent.