Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.

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The mechanisms of pathogenesis driving alpha-gal syndrome (AGS) are not fully understood. Differences in immune gene expression between AGS individuals and non-allergic controls may illuminate molecular pathways and targets critical for AGS development. We performed immune expression profiling with RNA from the peripheral blood mononuclear cells (PBMCs) of seven controls, 15 AGS participants, and two participants sensitized but not allergic to alpha-gal using the NanoString nCounter PanCancer immune profiling panel, which includes 770 genes from 14 different cell types. The top differentially expressed genes (DEG) between AGS subjects and controls included transcription factors regulating immune gene expression, such as the NFκB pathway (NFKBIA, NFKB2, REL), antigen presentation molecules, type 2/allergic immune responses, itch, and allergic dermatitis. The differential expression of genes linked to T and B cell function was also identified, including transcription factor BCL-6, markers of antigen experience (CD44) and memory (CD27), chemokine receptors (CXCR3, CXCR6), and regulators of B-cell proliferation, cell cycle entry and immunoglobulin production (CD70). The PBMCs from AGS subjects also had increased TNF and IFN-gamma mRNA expression compared to controls. AGS is associated with a distinct gene expression profile in circulating PBMCs. DEGs related to antigen presentation, antigen-experienced T-cells, and type 2 immune responses may promote the development of alpha-gal specific IgE and the maintenance of AGS.

RATIONALE: Recent retrospective research associated early life acid suppressive medication with food allergies. We sought to prospectively evaluate the association between acid suppressive medication in infancy and development of IgE-mediated food allergy in early childhood. METHODS: The Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) Study is an ongoing prospective observational cohort study of 1003 healthy newborn infants designed to evaluate the development of food allergies in their first 3 years of life. IgE-mediated food allergy was determined by independent agreement of two allergist reviewers based on clinical reactivity and documented IgE sensitivity. RESULTS: 797 infants were analyzed (46% female, 89% term, 31% delivered via caesarian-section, 8% neonatal antibiotics) with a current median age of 36 [19, 54] months. 153 (19%) were exposed to acid suppressive medication, 45 (5%) were exposed to a proton pump inhibitor and 115 (13%) were exposed to a histamine-2 receptor antagonist, in their first six months of life. To date, 51 (6%) of children have developed a confirmed or probable IgE-mediated food allergy, most commonly to egg, peanut, tree nuts, and milk. Use of acid suppressive medication in the first six months of life was not associated with development of IgE-mediated food allergy in early childhood (OR 0.77 [0.31, 1.71], p50.59). CONCLUSIONS: Contrary to a recent retrospective report, early exposure to acid suppressive medication is not prospectively associated with development of IgE-mediated food allergy by age 3 in this cohort. J ALLERGY CLIN IMMUNOL FEBRUARY 2019 AB252 Abstracts MONDAY

Clinic, Rochester, MN, 4 Reading hospital-Tower Health System, West Reading, PA, 5 Division of Pediatric and Adult Allergy / Immunology, Mayo Clinic, Rochester, MN. RATIONALE: IVIG (Intravenous Immunoglobulin) and SCIG (Subcutaneous Immunoglobulin) have been regarded as therapeutically equivalent treatments for primary immunodeficiency diseases (PIDDs). IgG trough level is used as a monitoring measure for infection prevention. A systematic review and meta-analysis was performed in patients with PIDD and relationship between IgG dosing, trough IgG levels with overall infection incidence were evaluated. METHODS: Medline, EMBASE, Cochrane, Central and Scopus were searched for studies published from Jan 2000-June 2018, fulfilling the inclusion criteria. DerSimonian and Laird random-effect method was used to pool difference of IgG trough levels. Random-effect meta-regression was used to evaluate infection incidence per 100 mg/dl IgG trough increase through IVIG and SCIG. RESULTS: Out of 24 observational studies included (1,426 patients), 11 compared IgG trough levels among SCIG and IVIG (mean difference: 73.4 mg/dl, 95% CI: 31.67-119.19 mg/dl, I 2 5 45%, p50.05), favoring SCIG. For every 100 mg/dl increase in trough, a linear trend of decreased incidence rates of infection was identified in SCIG patients (p50.03), but no similar trend was identified in trough levels vs. infection rates for patients receiving IVIG (p50.67). CONCLUSIONS: SCIG is associated with a higher IgG trough level in comparison to IVIG. Higher SCIG troughs were associated with lower infection rates, while IVIG troughs demonstrated no relationship. Abstracts AB205 SUNDAY