A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes.

Background: Peanut allergy is the leading cause of food-related anaphylaxis, and accidental exposures are common. Oral immunotherapy (OIT) has been posited as a potential treatment. Methods: Patients aged 3–65 years with peanut-specific IgE ≥7 kU/l and/or a positive skin prick test with a history of an allergic reaction to peanut were recruited to undergo an OIT protocol. All adverse reactions were recorded by research staff or patients in real time. Results: Twenty-four patients received 6,662 doses. Symptoms were mostly mild (84%), and only 3 severe gastrointestinal reactions required the administration of epinephrine. Abdominal pain was the most common reaction, followed by oropharyngeal and lip pruritus. Respiratory symptoms were rare. Conclusions: In this trial of OIT in adults and children, most reactions were mild.

Aims-To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens.Study design-Prospective study. Methodology-We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria.Results-Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication.Conclusion-These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).

The mammalian target of rapamycin (mTOR) pathway contributes to various immunoinflammatory processes. Yet, its potential involvement in basophil responses in allergy remains unclear. In this pilot study, we quantified two key mTOR effector phosphoproteins, the eukaryotic initiation factor 4E (peIF4E) and S6 ribosomal protein (pS6rp), in blood basophils from nut allergy patients (NA, N= 16) and healthy controls (HC, N= 13).Without stimulation in vitro, basophil peIF4E levels were higher in NA than HC subjects (P=0.014). Stimulation with nut (offending) but not chicken / rice (non-offending) extract increased basophil peIF4E and pS6rp levels (+32%, P=0.018, and +98%, P=0.0026, respectively) in NA but not HC subjects, concomitant with increased surface levels of CD203c and CD63, both known to reflect basophil activation. Pre-treatment with the mTOR inhibitor rapamycin decreased pS6rp and CD203c responses in nut extract-stimulated basophils in NA subjects. Thus, basophil responses to offending allergens are associated with modulation of mTOR effector phosphoproteins.

RationaleOur main focus in the laboratory is to understanding the mechanisms of how oral immunotherapy (OIT) improves outcomes in patients. In this study, we aimed to determine if OIT is specific only to the food allergens administered in OIT or also to other offending allergens (i.e. "bystander effect"). To accomplish our aim, we studied T cell reactivity (i.e. proliferation assays) and T cell specificity (i.e. tetramer assays with peanut peptides) in both effector T cell (CD4+CD25neg) or Teff and regulatory T cell (CD4+CD25hiFoxp3+) or Treg subsets. MethodsA phase I trial of oral immunotherapy for peanut allergy was approved by the Stanford IRB and conducted according to ICH guidelines. All subjects (n=24) had a moderate to severe clinical reactions to peanut ingestion, peanut-specific IgE ≥ 15 kU/L, and a positive skinprick test. Subjects underwent an initial dose escalation to a maximum dose prior to initiating daily home dosing with q2wk dose. Blood samples were collected at baseline and throughout the course of the treatment. T cells were magnetically purified and tested for specificity to peanut epitopes, other offending food allergens for the patient, and a control antigen. Basophil reactivity was also assessed using a whole blood assay. Clinical assessments were performed using Bock's criteria. ResultsTwenty-four subjects, ages 5 to 45, have received 3777 doses. Teff cell proliferation (using 3H thymidine assays) was optimally suppressed by autologous Treg when activation occurred using antigen presenting cells (APCs) loaded with peanut, rather than loaded with other offending food allergens (i.e. milk). Basophil reactivity (as determined by CD203c) was downregulated during the course of OIT to both peanut and other offending allergens. ConclusionsWe report on our immune monitoring results to date at Stanford Hospital and Clinics with a phase I peanut oral immunotherapy study using published methods. With T cell monitoring, we were able to show downregulation of specific peanut-induced proliferation and that this downregulation was mediated by Treg specific to peanut epitopes.

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Background-Peanut allergy is the leading cause of food-related anaphylaxis and accidental exposures are common. Oral immunotherapy has been posited as a potential treatment.

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