TY - JOUR
T1 - The false alarm hypothesis
T2 - Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins
AU - Smith, Peter K.
AU - Masilamani, Madhan
AU - Li, Xiu Min
AU - Sampson, Hugh A.
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2017/2/1
Y1 - 2017/2/1
N2 - The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of “alarmins.” Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the “false alarm” hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.
AB - The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of “alarmins.” Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the “false alarm” hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.
KW - Food allergy
KW - advanced glycated end-products
KW - alarmins
KW - glycation
KW - receptor for advanced glycated end-products
UR - http://www.scopus.com/inward/record.url?scp=84995938563&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2016.05.040
DO - 10.1016/j.jaci.2016.05.040
M3 - Article
C2 - 27544741
AN - SCOPUS:84995938563
SN - 0091-6749
VL - 139
SP - 429
EP - 437
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -