Jeffrey D. Miller

Chemical treatment of carpets to reduce allergen: A detailed study of the effects of tannic acid on indoor allergens

Tannic acid (TA), a protein-denaturing agent, has been reported to reduce allergen levels in house dust and is marketed for that purpose as 1% and 3% solutions. We investigated the effects of TA on dust allergens by using monoclonal antibody-based ELISAs for mite (Der p I, Der f I, and group II) and cat (Fel d I) allergens. Initial studies confirmed that TA reduced allergen levels in carpet dust. However, when dust samples from treated carpets are extracted in saline solution, residual TA redissolves and may interfere with the assessment of allergens. In the laboratory, concentrations of TA as low as 0.1% inhibited the assays, but this effect may be prevented by addition of 5% bovine serum albumin (BSA). After treatment of dust samples in the laboratory with 3% TA, the apparent reductions in Der p I and Der f I levels were 89% and 96%, respectively, but when the samples were extracted in 5% BSA the reductions were 74% and 92%. Similar effects were seen with dust samples from carpets treated with TA. In an extreme case in which a carpet had been repeatedly treated with TA, the apparent concentration of Der p I was < 0.05 microgram/gm without BSA and 2.1 and 8.4 microgram/gm when extracted in the presence of 1% and 5% BSA, respectively. Our testing of the ability of TA to denature Fel d I demonstrated an 80% reduction in allergen, but only in samples with an initial concentration of less than 200 micrograms Fel d I/gm dust.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of homogenization might explain the benefits of raw cow's milk

In their correspondence, they state that one potential explanation for the apparent discrepancy in the data is that they used primary BECs and we used a BEC cell line. While we did use the A549 cell line for some studies, we show in Fig 2D (RSV infection) and supplemental Fig 1, E (SeV infection), that siRNAmediated knockdown of RIG-I in normal human bronchial epithelial (NHBE) cells inhibited approximately 90% of the TSLP gene induction. Also, we showed that NF-kB could be ChIP’d from 2 sites in the TSLP gene promoter following viral infection of these same cells (supplemental Fig 2). We had previously defined these NF-kB sites as important for the induction of TSLP gene expression by IL-1b or TNF-a treatment of NHBE cells. Thus, we have shown that RIG-I–induced activation of NF-kB is critical for TSLP gene induction in BECs. We have also used siRNA knockdown of TLR3 and TLR4 in NHBEs and have found that the knockdown of each individually leads to an approximately 40% to 50% reduction in RSV-mediated TSLP gene induction (Lee and Ziegler, unpublished results). The TLR3 result is consistent with the finding that RIG-I activation induces TLR3 gene expression. By using both constitutively active IRF3 or IRF 7 (Fig 3) or dominant negative IRF3 or IFR7 (data not shown), we could find no role for these factors in respiratory virus induction of TSLP in BECs. Steven F. Ziegler, PhD

Additional effects of dietary advanced glycation end products

To the Editor: The excellent review by Smith et al makes a convincing case for the contribution of dietary advanced glycation end products (AGEs) to the development of food allergy. There is also additional evidence that AGEs may be involved in asthma. Induced sputum levels of the AGE pentosidine are higher in patients with asthma than in those without asthma, and increase with age at a markedly faster rate in patients with asthma than in controls, such that they are higher in young patients with asthma than in old people without asthma. In contrast to most tissues, where the receptor for advanced glycation endproducts (RAGE) is low or absent unless specifically upregulated, RAGE is present on eosinophils and in upper and lower airways, and at particularly high levels in the airways of patients with chronic obstructive pulmonary disease. In addition, there is at least 1 instance in which an allergy to a pharmaceutical results from the formation of immunogenic AGE epitopes on the drug. The negative effects of AGEs are not limited to allergy. There is strong evidence of a causal relationship between AGEs and aging, so much so that the beneficial effects of caloric restriction on decreasing oxidative stress and increasing longevity in mice are reversed when the restricted-calorie diet is modified to also be high in AGEs. AGEs do not appear on the list of ingredients printed on packaged foods. Anyone interested in eating a healthful diet that is not proinflammatory would do well to consider the hightemperature cooking that creates these immunoreactive compounds. Jeffrey D. Miller, MD

An evolutionary perspective on intestinal lymphatic fat absorption, the industrialization of food, and allergy

Never-theless, although dietary fat has been implicated in vascular andinflammatorydiseases,thepossibleroleoftheabsorptionoffatsintotheintestinallymphaticsystemhasnotbeenemphasizedregardingallergy.Furthermore,thislipid-absorptivesystemisnowconfrontedwith a diet of mechanically processed foods, the lipid componentsof which have been fractionated, concentrated, emulsified, andotherwise radically modified from the state present during thegastrointestinal and immune systems’ evolutionary selection.Dietary LipidsFatty acids comprise a hydrophilic carboxyl (COOH) groupattached to a hydrophobic linear hydrocarbon chain and are cate-gorized according to their number of carbons as short-chain ( 12 car-bons)fattyacids.Fatsaretri-estersof thetri-alcoholglycerolwith3fatty acids (ie, triglycerides). Fats that are liquid at room tempera-ture are called oils. Most foods, including peanuts, egg, and milk,contain predominantly long-chain fatty acids.There is an important distinction between the absorption oflong-chain fats and the absorption of other food products. Digestedproteins, carbohydrates, and short- and medium-chain tri-glycerides are primarily absorbed into the portal circulation, pass-ing through the liver and then rapidly into the systemic circulation.In contrast, long-chain triglycerides are absorbed into the lactealsand formed into lipoproteins such as chylomicrons, which thenspend approximately 4 hours in contact with the mesenteric im-mune system before reaching the systemic circulation through thethoracic duct.

Possible contribution of decreased phytoprostanes to diet-induced improvements in aspirin exacerbated respiratory disease

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The Role of Dust Mites in Allergy

House dust mites are an unsurpassed cause of atopic sensitization and allergic illness throughout the world. The major allergenic dust mites Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, and Blomia tropicalis are eight-legged members of the Arachnid class. Their approximately 3-month lifespan comprises egg, larval, protonymph, tritonymph, and adult stages, with adults, about one fourth to one third of a millimeter in size, being at the threshold of visibility. The geographic and seasonal distributions of dust mites are determined by their need for adequate humidity, while their distribution within substrates is further determined by their avoidance of light. By contacting the epithelium of the eyes, nose, lower airways, skin, and gut, the allergen-containing particles of dust mites can induce sensitization and atopic symptoms in those organs. Various mite allergens, contained primarily in mite fecal particles but also in shed mite exoskeletons and decaying mite body fragments, have properties that include proteolytic activity, homology with the lipopolysaccharide-binding component of Toll-like receptor 4, homology with other invertebrate tropomyosins, and chitin-cleaving and chitin-binding activity. Mite proteases have direct epithelial effects including the breaching of tight junctions and the stimulation of protease-activated receptors, the latter inducing pruritus, epithelial dysfunction, and cytokine release. Other components, including chitin, unmethylated mite and bacterial DNA, and endotoxin, activate pattern recognition receptors of the innate immune system and act as adjuvants promoting sensitization to mite and other allergens. Clinical conditions resulting from mite sensitization and exposure include rhinitis, sinusitis, conjunctivitis, asthma, and atopic dermatitis. Systemic allergy symptoms can also occur from the ingestion of cross-reacting invertebrates, such as shrimp or snail, or from the accidental ingestion of mite-contaminated foods. Beyond their direct importance as a major allergen source, an understanding of dust mites leads to insights into the nature of atopy and of allergic sensitization in general.