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Abstract

Because house dust mites (HDMs) are found in the environment, they are mostly considered as a source of allergens involved in respiratory allergies. The works from Sanchez-Borges et al1Sánchez-Borges M. Capriles-Hullet A. Oral exposure to mite allergens: sensitizer or tolerogenic?.J Allergy Clin Immuol. 2019; 143: 808Abstract Full Text Full Text PDF Scopus (1) Google Scholar and others have demonstrated that HDMs can contaminate food, which can trigger allergic reactions including severe manifestations such as grade 4 anaphylaxis on its ingestion.2Sanchez-Borges M. Capriles-Hulett A. Fernandez-Caldas E. Suarez-Chacon R. Caballero F. Castillo S. et al.Mite-contaminated foods as a cause of anaphylaxis.J Allergy Clin Immunol. 1997; 99: 738-743Abstract Full Text PDF PubMed Scopus (111) Google Scholar, 3Blanco C. Quiralte J. Castillo R. Delgado J. Arteaga C. Barber D. et al.Anaphylaxis after ingestion of wheat flour contaminated with mites.J Allergy Clin Immunol. 1997; 99: 308-313Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 4Takahashi K. Taniguchi M. Fukutomi Y. Sekiya K. Watai K. Mitsui C. et al.Oral mite anaphylaxis caused by mite-contaminated okonomiyaki/pancake-mix in Japan: 8 case reports and a review of 28 reported cases.Allergol Int. 2014; 63: 51-56Abstract Full Text PDF PubMed Scopus (29) Google Scholar These acute reactions are observed in patients who are already sensitized to HDMs. Our work further highlights that the first step for the development of allergy toward HDMs, that is, allergic sensitization, can be induced by oral exposure to HDMs through breast milk. We demonstrated a causal effect in a mouse experimental model5Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar and an association with increased sensitization risk in a birth cohort.6Baiz N. Macchiaverni P. Tulic M.K. Rekima A. Annesi-Maesano I. Verhasselt V. EDEN Mother-Child Cohort Study GroupEarly oral exposure to house dust mite allergen through breast milk: a potential risk factor for allergic sensitization and respiratory allergies in children.J Allergy Clin Immunol. 2017; 139: 369-372.e10Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Altogether, these works strongly suggest that oral exposure to HDMs can be a cause for both sensitization and allergic reaction to HDMs. Two factors may be critical for the induction of tolerance to HDM allergens transferred through breast milk: the dose and the biochemical characteristics of the allergen. Liu et al7Liu H.C. Pai S.Y. Cheng W.T. Chen H.L. Tsai T.C. Yang S.H. et al.Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness.Allergy Asthma Clin Immunol. 2013; 9: 21Crossref PubMed Scopus (9) Google Scholar showed that transgenic milk containing Der p 2 at a concentration of mg/mL could protect from allergy, that is, 1 million times higher as compared with the physiological levels of allergens found in human milk, including Der p 1, and in the experimental setting we used.5Macchiaverni P. Rekima A. Turfkruyer M. Mascarell L. Airouche S. Moingeon P. et al.Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.Allergy. 2014; 69: 395-398Crossref PubMed Scopus (38) Google Scholar, 6Baiz N. Macchiaverni P. Tulic M.K. Rekima A. Annesi-Maesano I. Verhasselt V. EDEN Mother-Child Cohort Study GroupEarly oral exposure to house dust mite allergen through breast milk: a potential risk factor for allergic sensitization and respiratory allergies in children.J Allergy Clin Immunol. 2017; 139: 369-372.e10Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar This suggests that nonphysiological high doses of HDM allergens may be required to induce oral tolerance in early life. In addition to the dose, the biochemical characteristics of the allergen may be key in the immune outcomes. As compared with Der p 2, many of the HDM allergens show protease activity, which has been shown to be critical for allergic sensitization through the respiratory tract. We further found that Der p proteases maintained their enzymatic activity in the digestive tract of adult mice and decreased the barrier function of gut tissue from healthy adults.8Tulic M.K. Vivinus-Nebot M. Rekima A. Rabelo Medeiros S. Bonnart C. Shi H. et al.Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction.Gut. 2016; 65: 757-766Crossref PubMed Scopus (50) Google Scholar We are currently investigating whether Der p proteases in maternal breast milk are causing allergic immune priming in the neonatal gut. We also seek how to manipulate Der p levels and its protease activity in breast milk, to induce tolerance to HDM allergens instead of allergic sensitization. Finally, we thank the authors for highlighting that we need to be cautious regarding the interpretation of our data, because some may conclude to recommend avoidance of breast-feeding for allergy prevention. Importantly, in addition to oral exposure through breast milk, infants are most probably orally exposed to HDMs present in their environment. Indeed, settled dust is found not only on toys that children put into their mouth but also contaminates water and food as highlighted by studies on exposure to airborne pollutant.9Custovic A. To what extent is allergen exposure a risk factor for the development of allergic disease?.Clin Exp Allergy. 2015; 45: 54-62Crossref PubMed Scopus (53) Google Scholar Furthermore, most inhaled protein is actually ingested because of the mucociliary clearance from the respiratory tract. Accordingly, we recently found that HDM Der p 1 allergen was present in digestive fluid of healthy adults.7Liu H.C. Pai S.Y. Cheng W.T. Chen H.L. Tsai T.C. Yang S.H. et al.Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness.Allergy Asthma Clin Immunol. 2013; 9: 21Crossref PubMed Scopus (9) Google Scholar Currently, no data exist on allergic outcomes in infants who are orally exposed to HDMs by direct exposure in the environment versus indirect exposure through breast milk. By elucidating which factors in breast milk are protective for allergy and how to modulate them, we will give breast milk the potential to prevent allergy, in addition to being the most efficient way to prevent infectious disease in children.10Victora C.G. Bahl R. Barros A.J. França G.V.A. Horton S. Krasevec J. et al.Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect.Lancet. 2016; 387: 475-490Abstract Full Text Full Text PDF PubMed Scopus (3335) Google Scholar Loss of an IgG plasma cell checkpoint in patients with lupusJournal of Allergy and Clinical ImmunologyVol. 143Issue 4PreviewIgG antinuclear antibodies (ANAs) are a feature of several autoimmune diseases. These antibodies arise through defects in central or peripheral tolerance checkpoints. The specific checkpoints breached in patients with autoimmune disease are not fully understood. Full-Text PDF