S250 Abstracts
Evaluation of IP Mouse Models for Assessing the Allergenic Potential of Proteins K. Thomas1, C. Herouet2, G. Bannon3, G. Ladics4, S. MacIntosh5, L. Privalle6, M. Woolhiser7; 1ILSI Health and Environmental Sciences Institute, Washington, DC, 2Bayer CropScience, Sophia Antipolis, FRANCE, 3Monsanto Company, St. Louis, MO, 4E.I. Dupont De Nemours and Company, Newark, DE, 5Bayer CropScience, Research Triangle Park, NC, 6BASF Plant Science, Research Triangle Park, NC, 7The Dow Chemical Company, Midland, MI. RATIONALE: The objective of this exercise was to evaluate the utility of mouse models for differentiating between allergens and putative nonallergens in the context of assessing novel proteins from biotechnology. METHODS: Known human allergenic proteins (peanut Ara h 1 and Ara h 2, cow’s milk -lactoglobulin [B-LG]) and putative non-allergenic proteins (spinach RUBISCO and soy lipoxygenase [SLG]) were purified to > 90% and provided to each laboratory. Each of four participating laboratories employed the intraperitoneal (ip) route of exposure using mouse strains including BALB/c, BDF-1, C3H/HeJ, A/J, and C57/Bl6 to evaluate the test proteins. Other experimental variables, which differed for each laboratory, included the presence or absence of adjuvant (i.e., alum), the number and length of time between ip injections, protein doses, and the use of homologous or heterologous PCA to assess IgE. One laboratory also systematically evaluated clinical signs. RESULTS: All the laboratories demonstrated significant PCA responses to RUBISCO in the absence of adjuvant. In two laboratories, the relative response via PCA to RUBISCO was significantly greater than the response to Ara h 2. In another laboratory, a much higher relative clinical score was seen with SLG than was seen with B-LG. In addition, the nature and magnitude of the responses varied considerably between the different mouse strains. CONCLUSIONS: In general, it was not possible to accurately differentiate between the known allergens and the putative non-allergens in any laboratory using the strains and endpoints evaluated. Further work appears necessary to evaluate the allergenic potential of proteins using mouse models. Funding: ILSI HESI
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Studies of Oral Mold Challenge in Mold Sensitive Subjects
S. Luccioli1, J. Malka-Rais1, T. M. Nsouli1, L. Chiazze2, J. A. Bellanti1; Center for Interdisciplinary Studies of Immunology, Georgetown University, Washington, DC, 2Georgetown University, Washington, DC. RATIONALE: Airborn mold or mold spores may be found in foods at low concentrations. It is unknown whether ingestion of these molds elicits hypersensitivity reactions in mold sensitive individuals. METHODS: Thirty four adult subjects with history of various allergic disorders, including asthma, were randomized into two groups depending on sensitivity by skin prick, intradermal or in vitro test to a mixed airborn mold preparation. Eighteen subjects were determined to be mold-sensitive; sixteen were non mold-sensitive. Subjects underwent a single blind, placebo-controlled oral challenge to increasing concentrations, ranging from 100 ng to 1 mg of individual mold, of the mixed mold preparation. This challenge protocol was chosen to potentially establish a symptom eliciting concentration of mold (SECM) at concentrations that commonly contaminate foods. Using a modified scoring system (MSS), 5 points were assigned for each organ system symptom elicited by the challenge. RESULTS: All subjects were able to tolerate the oral dose challenges to the final mold concentration. However, there was a noted difference in MSS score (+ SEM) between mold sensitive (8.6 + 1.6) and non moldsensitive (2.2 + 0.8) subjects, p=0.001. Furthermore, an inverse relationship was seen between SECM and degree of dermal reactivity to molds. CONCLUSIONS: Compared to non mold-sensitive individuals, moldsensitive subjects experienced higher symptom scores after oral mold challenge at low concentrations. The results of these studies suggest that ingestion of molds, at concentrations potentially found in foods, may pro1International
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
voke hypersensitivity reactions in mold allergic patients and should be considered a contributing factor to allergic symptoms in mold sensitive individuals. Funding: Immunology Center at Georgetown
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Influenza Vaccine in 55 Patients With Egg Allergy
M. J. Dorsey, L. Song, T. Geha, A. Timmons, H. Oettgen, L. Schneider; Division of Immunology, Children’s Hospital of Boston, Boston, MA. RATIONALE: Egg allergy prevents many patients from receiving influenza vaccine. Clinical predictors of vaccine reaction might help in determining safety of administration. METHODS: 55 patients diagnosed with egg allergy confirmed by positive SPT and/or egg specific IgE underwent skin testing for flu vaccine. Patients with negative SPT received vaccine; those with positive SPT had vaccine administration deferred in most cases. Clinical and laboratory profiles were obtained to include asthma history, presence of other food allergy, and level of egg specific IgE. ELISA was conducted on selected vaccine lots to determine ovalbumin concentration. RESULTS: Clinical history of egg allergy ranged from eczema to wheezing. 45/55 patients had asthma and 52/55 had other food allergy. 32/55(58%) had negative SPT and 23/55(42%) had positive SPT. All 32 patients who were SPT negative to vaccine were immunized with 4 patients developing mild localized cutaneous reactions and 1 patient developing mild wheezing. Of the 23 patients who were SPT positive to vaccine 5 were immunized and none developed reactions. Detected ovalbumin concentration in three vaccine lots ranged from 4.9 ug/mL to 14.6 ug/mL. CONCLUSIONS: In our study patients with egg allergy were safely immunized with influenza vaccine. Current recommendations for influenza vaccine and egg allergy remain the safest and most reliable approach to administration (Zeiger RS. Current issues with influenza vaccination in egg allergy. JACI 2002;110:830-40).
TUESDAY
A Case of Angioedema Following the Administration of Recombinant Tissue Plasminogen Activator S. S. Mohan1, I. Veksler-Offengenden2; 1Medicine/Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Allergy and Immunology, SUNY Stony Brook, Stony Brook, NY. RATIONALE: Serious allergic reactions have been observed during thrombolytic therapy with recombinant tissue plasminogen activator (rTPA) which is used in the treatment of acute ischemic stroke. Angioedema, a well-known complication of angiotensin-converting enzyme inhibitor (ACE-I), has been reported with increasing frequency in patients receiving rTPA. METHODS: We describe a case of angioedema associated with the administration of rTPA in a patient experiencing an acute ischemic stroke while on chronic ACE-I therapy. RESULTS: A 65-year-old woman with a history of hypertension developed acute right-sided weakness and numbness. Her hypertension was previously treated with lisinopril for more than a year without adverse reactions. Neurological evaluation and head CT were consistent with a diagnosis of acute ischemic stroke. rTPA was administered with progressive improvement of her motor strength and sensation. Approximately thirty minutes after receiving rTPA, the patient developed lip tingling and right-sided lip swelling. There was no associated respiratory difficulty, rash, or dysphagia. The ACE-I was discontinued, and the patient was treated with antihistamines and corticosteroids. The patient’s symptoms resolved completely within 24 hours. CONCLUSIONS: Recent studies suggest angioedema is more frequent in patients treated with rTPA while on ACE-I. ACE-Inhibitors decrease the breakdown of bradykinins while rTPA increases their production. These elevated bradykinin levels are thought to be responsible for vasodilatation and enhanced permeability of capillaries and venules as seen in angioedema. Patients on chronic ACE-I therapy should be closely monitored when receiving rTPA since their concomitant use can lead to life threatening adverse reactions such as angioedema.
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