Dr. Ron’s Research Review – April 8, 2020

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This week’s research review focuses on adult-onset food allergy.

Adult-Onset Food Allergy

Prevalence of food sensitization among adults is high. In the United States, it was reported to be 14.9% in 2010. At the same time, physician-diagnosed food allergy was reported to be 6.5%. (Verrill et al., 2015)
Seafood allergy is one of the more frequent causes of food allergy in adults. On the basis of a recent meta-analysis, in the United States the prevalence of self-reported shellfish allergy in adults ranged from 1.7% to 9.0%, and the prevalence of self-reported fish allergy ranged from 0.0% to 7.0%.  (Moonesinghe et al., 2016)
The 5 most common food allergies in adults determined, in decreasing order of frequency, were shellfish (54%), tree nut (43%), non-shell fish (15%), soy (13%), and peanut (9%). Twenty-eight of 171 patients (16.4%) were determined to be allergic to more than 1 food. (Kamdar et al., 2015)

Anti-Acid Medication

An observational cohort study screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically.
Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. Anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients. (Untersmayr et al., 2005)

Gastric Acid

Gastric acid levels determine the activation of gastric pepsin and also the release of pancreatic enzymes. When anti-ulcer drugs inhibit or neutralize gastric acid, they allow persistence of intact food allergens and protein-bound oral drugs with enhanced capacity to sensitize and elicit allergic reactions via the oral route. (Pali-Schöll and Jensen-Jarolim, 2011)
Hindrance of gastric digestion by elevation of the gastric pH, the therapeutic goal of anti-ulcer medication, was recently shown to trigger food allergy via oral sensitization in a murine food allergy model. The relevance in humans was assessed in an observational study of 152 gastroenterological patients who were medicated with anti-ulcer drugs due to dyspeptic disorders. Twenty-five percent of all patients developed a boost or de-novo IgE formation towards regular constituents of the daily diet. The clinical relevance of the induced antibodies was confirmed by positive skin and oral-provocation tests. Moreover, the importance of gastric digestion was also proven for food-allergic patients, as the allergenicity of allergens were reduced up to a 10,000-fold by gastric digestion. (Untersmayr and Jensen-Jarolim, 2006)

 

Dr. Ron

 


Articles

 

Prevalence and characteristics of adult-onset food allergy.
            (Kamdar et al., 2015) Download
Although it is common for childhood food allergies to milk, egg, soy, or wheat to be outgrown, those to fish or shellfish have been suggested to develop in adulthood and/or to persist. Here, our primary objective was to determine the prevalence of adult-onset food allergy, with secondary objectives of examining the characteristics of these patients further, including the assessment of additional common allergens. By using the Northwestern Medicine Enterprise Data Warehouse, medical records of patients who were seen by allergy physicians at the Northwestern University adult allergy clinics and who received a diagnosis of food allergy underwent retrospective chart review. From 1111 charts assessed, 171 cases were determined to meet the age-restricted inclusion criteria, which suggests that at least 15% of patients with an initial food allergy diagnosis code were adult-onset food allergy.

Anti-acid medication as a risk factor for food allergy.
            (Pali-Schöll and Jensen-Jarolim, 2011) Download
An important feature for oral allergens is their digestion-resistance during gastrointestinal transit. For some oral allergens, digestion stability is an innate feature, whereas digestion-labile antigens may only persist in times of impairment of the digestive system. In this review, we collect evidence from mouse and human studies that besides the inherent molecular characteristics of a food protein, the stomach function is decisive for the allergenic potential. Gastric acid levels determine the activation of gastric pepsin and also the release of pancreatic enzymes. When anti-ulcer drugs inhibit or neutralize gastric acid, they allow persistence of intact food allergens and protein-bound oral drugs with enhanced capacity to sensitize and elicit allergic reactions via the oral route. Mouse studies further suggest that maternal food allergy arising from co-application of a food protein with anti-acid drugs results in a Th2-biased immune response in the offspring. Especially, anti-ulcer drugs containing aluminum compounds act as Th2 adjuvants. Proton pump inhibitors act on proton secretion but also on expression of the morphogen Sonic hedgehog, which has been related to the development of atrophic gastritis. On the other hand, atrophic gastritis and resulting hypoacidity have previously been correlated with enhanced sensitization risk to food allergens in elderly patients. In summary, impairment of gastric function is a documented risk factor for sensitization against oral proteins and drugs.


 

Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.
            (Untersmayr et al., 2005) Download
Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients.

The effect of gastric digestion on food allergy.
            (Untersmayr and Jensen-Jarolim, 2006) Download
PURPOSE OF REVIEW:  The role of the stomach as the primary location of protein digestion is very well recognized, leading to classification of proteins as digestion-resistant or digestion-labile. This review analyses the role of gastric digestion in food allergy. RECENT FINDINGS:  Hindrance of gastric digestion by elevation of the gastric pH, the therapeutic goal of anti-ulcer medication, was recently shown to trigger food allergy via oral sensitization in a murine food allergy model. The relevance in humans was assessed in an observational study of 152 gastroenterological patients who were medicated with anti-ulcer drugs due to dyspeptic disorders. Twenty-five percent of all patients developed a boost or de-novo IgE formation towards regular constituents of the daily diet. The clinical relevance of the induced antibodies was confirmed by positive skin and oral-provocation tests. Moreover, the importance of gastric digestion was also proven for food-allergic patients, as the allergenicity of allergens were reduced up to a 10,000-fold by gastric digestion. SUMMARY:  These recent studies indicate for the first time the important gate-keeping function of gastric digestion, both in the sensitization and the effector phases of food allergy.


 

References

Kamdar, TA, et al. (2015), ‘Prevalence and characteristics of adult-onset food allergy.’, J Allergy Clin Immunol Pract, 3 (1), 114-5.e1. PubMed: 25577631
Moonesinghe, H, et al. (2016), ‘Prevalence of fish and shellfish allergy: A systematic review.’, Ann Allergy Asthma Immunol, 117 (3), 264-272.e4. PubMed: 27613460
Pali-Schöll, I and E Jensen-Jarolim (2011), ‘Anti-acid medication as a risk factor for food allergy.’, Allergy, 66 (4), 469-77. PubMed: 21121928
Untersmayr, E, et al. (2005), ‘Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.’, FASEB J, 19 (6), 656-58. PubMed: 15671152
Untersmayr, E and E Jensen-Jarolim (2006), ‘The effect of gastric digestion on food allergy.’, Curr Opin Allergy Clin Immunol, 6 (3), 214-19. PubMed: 16670517
Verrill, L, R Bruns, and S Luccioli (2015), ‘Prevalence of self-reported food allergy in U.S. adults: 2001, 2006, and 2010.’, Allergy Asthma Proc, 36 (6), 458-67. PubMed: 26453524