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Introduction In 2019, 5.3 million liveborn children died before 5 years of age worldwide, nearly half of whom died from infectious diseases, including lower respiratory infections and diarrhea (1). The [...], BACKGROUND. The use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations. METHODS. Using multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens. RESULTS. The antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection. CONCLUSION. This comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality. FUNDING. Bill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP). more...

Introduction IgE-mediated food allergy affects 6%-8% of children, and although allergies to foods such as milk or egg are frequently outgrown, allergies to peanut are commonly lifelong and affect 1%-2% [...], Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the atopic dermatitisassociated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life. more...

Background: Anaphylaxis is an acute, systemic allergic reaction that can be life threatening, and with an increasing incidence and costs associated with hospitalization and intensive care. Objective: To assess the risk factors for hospitalization by comparing pediatric and adult patients. Methods: We performed a retrospective chart review for patients with anaphylactic reactions who presented to the Albany Medical Center emergency department between 2005 and 2012. Results: We identified 267 anaphylactic reactions in 258 patients (143 adults). Of those, 128 (48%) were not coded as anaphylaxis despite fulfilling diagnostic criteria. Foods were the most common trigger both in adults and children. Factors associated with increased odds of hospitalization (intensive care unit [ICU] and hospital floor combined) included a severity score of 3 in both children (odds ratio [OR] 41.86 [95% confidence interval {CI}, 2.9 - 602.48], p = 0.006) and adults (OR 32.52 [95% CI, 6.28-168.35], p < 0.001), and those who received multiple doses of epinephrine in children (OR 15.36 [95% CI, 1.9-121.4], p = 0.009) and adults (OR 11.49 [95% CI, 3.08-44.13], p < 0.001). Patient characteristics associated with ICU admission in children and adults combined included Medicare and/or Medicaid insurance (OR 4.96 [95% CI, 1.14-21.67], p = 0.023), cutaneous symptoms (OR 0.19 [95% CI, 0.04-0.79], p = 0.23), and cardiovascular symptoms (OR 5.8 [95% CI, 1.16-28.87], p = 0.032). Conclusion: Anaphylaxis remains underrecognized and improperly treated in the emergency department. Severity of symptoms and receiving multiple doses of epinephrine were associated with hospitalization in both children and adults. Medicare and/or Medicaid insurance, and cardiovascular or cutaneous symptoms were characteristics associated with ICU admission in our cohort. [ABSTRACT FROM AUTHOR] more...