Potential role of advanced glycation end products in the TH2 adjuvant effect of peanut protein

Abstract

Ruiter et al showed that peanut protein induces a TH2 response by eliciting retinaldehyde dehydrogenase production in myeloid antigen-presenting cells.1Ruiter B. Smith N.P. Fleming E. Patil S.U. Hurlburt B.K. Maleki S.J. et al.Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.J Allergy Clin Immunol. 2021 Jul; 148: 182-194.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Noting that such an effect can also be produced by pathogen-associated molecular patterns, Ruiter et al1Ruiter B. Smith N.P. Fleming E. Patil S.U. Hurlburt B.K. Maleki S.J. et al.Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.J Allergy Clin Immunol. 2021 Jul; 148: 182-194.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar excluded the possibility that the effect was produced by endotoxin or aflatoxin. However, they did not exclude the possible role of advanced glycation end products (AGEs). AGEs are created during the browning of foods, including during the roasting of peanuts, and they contribute to peanuts’ allergenicity.2Maleki S.J. Chung S.Y. Champagne E.T. Raufman J.P. The effects of roasting on the allergenic properties of peanut proteins.J Allergy Clin Immunol. 2000; 106: 763-768Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar AGEs activate the same receptor (receptor for advanced glycation end products [RAGE]) as does the damage-associated molecular pattern HMGB1.3Smith P.K. Masilamani M. Li X.M. Sampson H.A. The false alarm hypothesis: food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins.J Allergy Clin Immunol. 2017; 139: 429-437Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Although some of the experiments reported by Ruiter et al1Ruiter B. Smith N.P. Fleming E. Patil S.U. Hurlburt B.K. Maleki S.J. et al.Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.J Allergy Clin Immunol. 2021 Jul; 148: 182-194.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar used raw peanut extract, key studies showing gene expression and enzyme production used an extract made from roasted peanuts. In addition to their deleterious effects in conditions ranging from asthma, atherosclerosis, and diabetes to aging and Parkinson disease,4Brandt E.B. Lewkowich I.P. RAGE-induced asthma: a role for the receptor for advanced glycation end-products in promoting allergic airway disease.J Allergy Clin Immunol. 2019; 144: 651-653Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar,5Uribarri J. Woodruff S. Goodman S. Cai W. Chen X. Pyzik R. et al.Advanced glycation end products in foods and a practical guide to their reduction in the diet.J Am Diet Assoc. 2010; 110: 911-916.e12Abstract Full Text Full Text PDF PubMed Scopus (783) Google Scholar AGEs have been hypothesized to be a root cause of food allergy.3Smith P.K. Masilamani M. Li X.M. Sampson H.A. The false alarm hypothesis: food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins.J Allergy Clin Immunol. 2017; 139: 429-437Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar An argument against the role of AGEs here is that they work via the stimulation of Toll-like receptor (TLR) 4, whereas in the study by Ruiter et al1Ruiter B. Smith N.P. Fleming E. Patil S.U. Hurlburt B.K. Maleki S.J. et al.Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.J Allergy Clin Immunol. 2021 Jul; 148: 182-194.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar signaling of the antigen-presenting cells occurred largely via TLR1 and TLR2. However, Ruiter et al1Ruiter B. Smith N.P. Fleming E. Patil S.U. Hurlburt B.K. Maleki S.J. et al.Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.J Allergy Clin Immunol. 2021 Jul; 148: 182-194.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar found that blocking TLR1/TLR2 reduced enzyme expression by 70%. Was the other 30% due to AGEs? Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cellsJournal of Allergy and Clinical ImmunologyVol. 148Issue 1PreviewPeanut is a potent inducer of proallergenic TH2 responses in susceptible individuals. Antigen-presenting cells (APCs) including dendritic cells and monocytes instruct naive T cells to differentiate into various effector cells, determining immune responses such as allergy and tolerance. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 149Issue 1PreviewWe thank Miller1 for his interest in our article “Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells,”2 which appeared in the July 2021 issue of the Journal of Allergy and Clinical Immunology. Miller1 raised the interesting point of a potential role of advanced glycation end products (AGEs) in the TH2 adjuvant effect of peanut protein. AGEs are present in raw peanuts, and their levels are increased during the process of roasting, which is known to contribute to peanuts’ allergenicity. Full-Text PDF