Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to F c ε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy requires a history of classic clinical symptoms and evidence of food-specific IgE by either skin-prick or serum-specific IgE testing. Symptoms of IgE-mediated food allergies range from mild to severe. The severity of symptoms is not predicted by the level of specific IgE or skin test wheal size, but the likelihood of symptom onset is directly related. Diagnosis is excluded when a patient can ingest the suspected food without clinical symptoms and may require an in-office oral food challenge if testing for food-specific IgE by serum or skin testing is negative or low. Anaphylaxis is the most severe form of the clinical manifestation of IgE-mediated food allergy, and injectable epinephrine is the first-line treatment. Management of food allergies requires strict avoidance measures, counseling of the family about constant vigilance, and prompt treatment of allergic reactions with emergency medications. Guidelines have changed recently to include early introduction of peanuts at 4-6 months of life. Early introduction is recommended to prevent the development of peanut allergy. Future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.

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RATIONALE: Striking class I HLA risk associations and CD8+ T cell dependency have been described for both Stevens-Johnson Syndrome/ toxic epidermal necrolysis (SJS/TEN) and abacavir hypersensitivity (AHS). However, distinct clinical phenotypes and positive predictive values (55% for HLA-B*57:01 restricted AHS and <8% for all HLA risk alleles and SJS/TEN) highlight key mechanistic differences. METHODS: Single cell technologies including T-cell receptor ab sequencing, multi-parameter flow cytometry, full transcriptome RNAseq, and mass cytometry were used to define the clonality and molecular signatures of pathogenic drug-specific T cells from paired PBMC, blister fluid, and acute, recovery, and patch test positive skin in SJS/TEN and AHS (n525). RESULTS: Dominant CD8+ T-cell clonotypes of effector memory phenotype (CCR7-) with variable expression of skin homing/residence markers (CLA, CD103) were seen in SJS/TEN skin and blister fluid and were present at much lower frequency in both acute and drug-stimulated recovery peripheral blood. A public TCR was dominant in blister fluid of HLA-B*15:02 restricted carbamazepine-SJS/TEN. For allopurinol SJS/ TEN, a dominant clonotype was identified in HLA-B*58:01+ blister fluid and a novel HLA class I restriction was identified with striking T-cell clonality (>97%) in blister fluid and skin. In contrast, for AHS, abacavir responsive CD8+ T cells with shared TCR clonotypes were isolated from the peripheral blood and positive patch tests that were polyclonal. CONCLUSIONS: Single cell approaches that define the signatures of drug-specific T cells in the skin and peripheral blood highlight mechanistic differences between HLA class I restricted drug hypersensitivity syndromes and will help drive the development of targeted therapeutics and screening approaches. 281 The increased risk of methicillin-resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy

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RATIONALE: Innate immune abnormalities and mitochondrial dysfunction are frequently reported in ASD subjects, indicating a possible association between immune-mediated inflammation and mitochondrial dysfunction in ASD. METHODS: Inflammatory cytokine such as IL-1ß generated by innate immune cells affect mitochondrial functions. In 71 ASD subjects, cytokine production by purified peripheral blood monocytes (PB Mo) and mitochondrial function measured as oxygen consumption rate (OCR) in peripheral blood mononuclear cells (PBMCs) were examined. RESULTS: A positive association between OCR and IL-1ß production was observed with TLR4 and TLR7/8 agonists in both ASD and controls. Because of variable responses to zymosan, a TLR2/6 agonist, ASD samples stimlated with zymosan were divided into three groups defined by the IL-1ß/IL-10 ratio results based on the reference values from 33 non-ASD controls. ASD cells with higher IL-1b/IL-10 ratio (N515) showed no association between OCR and IL-1b production. Cells with lower IL-1b/ IL-10 ratio (N57) showed a negative association, while those with normal IL-1b/IL-10 ratios (N549) revealed a positive association (r5-0.506 vs. 0.37, r5-0.466 vs. 0.344 for ATP linked and maximal OCR, respectively, for these 2 groups). Non-ATP linked OCR which is associated with oxygen burst revealed the similar tendency in these 2 groups (r5-0.455 vs. 0.385). ASD subjects with higher or lower IL-1b/IL-10 ratio with zymosan had chronic gastrointestinal (GI) symptoms. CONCLUSIONS: Our results indicates an association between IL-1ß production by innate immune cells and mitochondrial function of immune cells. Altered its association in some ASD subjects may be associated with their chronic GI symptoms.