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Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait found in 4% to 6% of the general population and defined by excess copies of alpha-tryptase at TPSAB1. Elevated basal serum tryptase (sBT >8 ng/mL) is a defining feature of HαT and appears to result from increased pro-alpha-tryptase synthesis and secretion rather than mast cell activation. It is estimated that approximately one-third of individuals with HαT have associated symptoms, including cutaneous, gastrointestinal, atopic, musculoskeletal, autonomic, and neuropsychiatric manifestations. HαT is found at a disproportionately high rate in systemic mastocytosis and idiopathic anaphylaxis, and is a modifying factor that independently increases the incidence and severity of anaphylaxis. The varied phenotypes associated with HαT may, in part, result from coinheritance of other genetic variants, increased expression of α-/s-tryptase heterotetramers, and/or overexpression of pro-alpha-tryptase, although further studies are needed. There is an accurate diagnostic test available to confirm HαT in patients that can be used in combination with sBT to help risk-stratify individuals in whom bone marrow biopsy is being considered. There is no specific treatment for symptoms associated with HαT, and management is focused on controlling clinical manifestations with mast cell mediator antagonists, aspirin, inhalers, epinephrine, omalizumab, and involvement of other specialists.

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic chronic rhinosinusitis with nasal polyps, asthma, and upper-/lower-respiratory tract reactions to nonsteroidal antiinflammatory drugs. Persistent, severe disease, anosmia, and alcohol sensitivity is typical. AERD is mediated by multiple pathways, including aberrant arachidonic acid metabolism leading to elevated leukotriene E4 and decreased prostaglandin E2. Mast cell mediators (prostaglandin D2) and unique properties of eosinophils and type 2 innate lymphoid cells, along with receptor-mediated signaling, also contribute to AERD pathogenesis. Pharmacologic therapies are a cornerstone of AERD treatment and include leukotriene modifiers, corticosteroids, biologics, and aspirin.

Rationale: There is little information regarding the allergen content of milk feeds in the preterm population. Previous studies have evaluated specific proteins/peptides via ELISA, but no studies have performed a broad analysis of the allergenic peptide content and protease activity of milk feeds in this population. Preterm infants spend a critical window of time for immune development in the Newborn Intensive Care Unit (NICU), and may receive fortified donor milk, maternal milk or formula feeds via nasogastric tube or bottle instead of fresh breastmilk via breastfeeding. Methods: To evaluate feasibility, we initially performed mass spectrometry on four human milk samples (two term and two preterm) from the Mommy’s Milk Human Milk Biorepository (HMB) which included maternal surveys of diet and environmental exposures. We analyzed the results against the University of Nebraska FASTA database and UniProt for a total of 2211 protein sequences. We then further analyzed 5 samples from the Microbiome, Atopy and Prematurity (MAP) pilot study along with formula and human milk fortifier controls and performed not only mass spectrometry, but also peptidomic and protease activity analysis. Results: Each HMB sample had between 806 and 1007 proteins, with 37 to 44 non-human proteins/sample encompassing 26 plant and animal species. Bovine proteins were the most numerous; seven unique Bos taurus proteins were found in all four samples, and three contained Bos d 5. Cat, dog, mosquito, salmon, and crab were detected in all four samples. All donors ingested fish, shellfish and tree nuts, and all had salmon and crab proteins in their milk samples; two almond proteins were detected in three samples. Aeroallergens, including dust mite (Der f 28, Der f 25) and mold (Cla h 4) were identified in all samples. Two samples contained allergens to latex (Hev b 9) and chicken (Gal d 10). One sample contained several unique proteins, including carrot, two molds (including Pen c 19) and Der f 33-like protein. In the preterm MAP samples, 784 digested non-human proteins were identified, 30 were non-bovine in origin. Proteins from 23 different species including aeroallergens, food, and contact allergens were identified. Protease activity was highest in human milk samples without human milk fortifier and lowest in preterm formula. Conclusions: These findings represent the first preterm milk feed mass spectrometry and protease analysis with identification of known allergenic proteins to food, contact and aeroallergens. The varying degree of protein detection may reflect variable individual secretion and augmentation of feeds. This raises questions of whether the composition of milk feeds in the NICU impact the development of atopic disease in the preterm population and whether the complex interaction between allergens, proteases, and other human milk components can serve to induce sensitization or tolerance to allergens in infants.

Background There is limited research investigating maternal dietary practices and health care provider recommendations when providing breast milk (BM) to children with immunoglobulin (Ig) E–mediated food allergy. Objective To explore health care provider recommendations and maternal practices when providing BM to children with IgE-mediated food allergy and to assess for possible IgE-mediated reactions to BM while the mother consumed the food to which her child has allergy. Methods A web-based survey was distributed to breastfeeding (BF) mothers of children with IgE-mediated food allergies. Reported reactions to BM were scored by an allergist, provided only with the details of the possible reaction and not the suspect allergen or route of exposure, as to the likelihood that the reaction was IgE mediated. Results A total of 133 mothers completed the survey. After food allergy diagnosis, 47.4% (n = 63) of the mothers reported that they were advised by their health care provider to continue BF without dietary restriction, 17.3% (n = 23) were advised to avoid eating the food(s) their child has allergy to while BF, and in 28.6% (n = 38), this concern was not addressed. A few of the mothers (12%, 16/133) reported that their child experienced an allergic reaction to BM. An allergist evaluated most of these reactions (75%, 12/16) as not likely IgE mediated. Conclusion This study exposed inconsistent recommendations for mothers providing BM to children with IgE-mediated food allergies. Most mothers were able to consume the food their child has allergy to without adverse sequelae. Standardized, evidence-based recommendations would enhance the well-being of these mother-infant dyads.