Paul J Bryce
Northwestern University At Chicago
Project start date: 2008-02-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
Regulation Of T Cell Migration By Histamine
Paul J Bryce
Medicinenorthwestern University
Grant 5R01AI076456-02 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Project start date: 2008-02-01
Project end date: 2013-01-31
Grants awarded to Paul J Bryce
A NOVEL MURINE MODEL OF FOOD ALLERGY TO PEANUT OR EGG
Paul J Bryce, Assistant Professor
Northwestern University, 750 N. Lake Shore Drive, 7th, Chicago, Il 60611
Grant 5R21AI078525-02 from National Institute Of Allergy And Infectious Diseases
Abstract: Food allergy affects approximately 11 million Americans and is escalating in prevalence. There are currently no available treatments and affected individuals are dependent on strict elimination diets and epinephrine to prevent the life-threatening reactions if accidental exposure occurs. Very little is known about the mechanisms that underlie the incidence, severity and spectrum of responses seen in food allergic patients. A significant reason for this has been the lack of an animal model that recapitulates the physiological and immunological features of food allergy. Previously utilized models are severely limited to specific strains of mice, large antigen doses or nonphysiological routes of immunization and have failed to elicit the hallmark immunological responses. We have developed a novel model using commonly used inbred mouse strains, antigen doses that are comparable to dietary levels and exposure via ingestion. Our model uses administration of food antigens (egg and peanut) concurrently with low amounts of Staphylococcus aureus enterotoxin B (SEB), a common food contaminant. This elicits immunological and physiological responses that mirror food allergic patients and represents a significant advance from other models. This proposal centers upon improving food allergy research in three directions optimization of our model (Aim 1), development of state-of-the-art physiological monitoring (Aim 2) and potential application to screening therapeutics (Aim 3). There aims are Aim 1 Establish the threshold levels of sensitizing antigen, SEB and challenging antigen doses. Aim 2 Develop methodology that will allow standardized, investigator independent, methods for monitoring physiological responses in our food allergy model. Aim 3 Test the effectiveness of a highly novel, bispecific antibody that inhibits IgE-mediated allergic responses in preventing anaphylaxis to peanut. We believe that these aims will facilitate our abilities to investigate the pathogenesis and immunological mechanisms underlying this disease and prove a novel, important tool for developing future therapies and clinical treatments
Keywords: 0-11 years old; 1, 2-Benzenediol, 4-(1-hydroxy-2-(methylamino)ethyl)-, (R)-; 21+ years old; 4-(1-Hydroxy-2-(methylamino)ethyl)-1, 2-benzenediol; ATGN; Accident and Emergency department; Acids; Administration, Oral; Adrenaline; Adult; Affect; Allergic; Allergy; Allergy to peanuts; Allergy, Food; American; Anaphylactic Reaction; Anaphylaxis; Animal Model; Animal Models and Related Studies; Antibodies, Bispecific; Antigens; Arts; Asthma; Atopic Dermatitis; Bifunctional Antibodies; Bispecific Antibodies; Bronchial Asthma; Cessation of life; Characteristics; Child; Child Youth; Childhood; Children (0-21); Clinical Treatment; Data; Death; Dermatitis, Atopic; Dermatitis, Eczematous; Development; Diabetes Mellitus, Brittle; Diabetes Mellitus, Insulin-Dependent; Diabetes Mellitus, Juvenile-Onset; Diabetes Mellitus, Ketosis-Prone; Diabetes Mellitus, Sudden-Onset; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type I; Diet; Disease; Disorder; Dose; Drug Administration, Oral; Eczema; Eczema, Atopic; Effectiveness; Emergency Department; Emergency room; Enterotoxins; Epi; Epinephrine; Family member; Fishes; Flare; Food; Food Contamination; Food Hypersensitivity; Future; Gastroenteritis; Generations; Groundnut Hypersensitivity; Groundnuts; Health Expenditures; Human, Adult; Human, Child; Hypersensitivity; IDD; IDDM; INFLM; IgE; Immune Globulins; Immune response; Immunization; Immunoglobulin E; Immunoglobulins; Immunoglobulins / Antibodies; Immunologic Stimulation; Immunological Stimulation; Immunostimulation; Inbred Strains Mice; Incidence; Individual; Inflammation; Ingestion; Injectable; Insulin-Dependent Diabetes Mellitus; Investigators; Left; Life; Light; Mammals, Mice; Meat; Mediating; Method LOINC Axis 6; Methodology; Methods; Mice; Mice, Inbred Strains; Milk; Modeling; Molecular; Monitoring, Physiologic; Monitoring, Physiological; Mouse Strains; Murine; Mus; Neurodermatitis, Atopic; Neurodermatitis, Disseminated; Oral Administration; Organism; Ovalbumin; Patch Tests; Pathogenesis; Patients; Peanut Hypersensitivity; Peanuts; Peanuts - dietary; Photoradiation; Physiologic; Physiologic Monitoring; Physiological; Prevalence; Process; Proteins; Psoriasis; QOL; Quality of life; Reaction; Research; Research Personnel; Researchers; Resistance; Rhinitis; Risk Factors; Route; S. aureus; S.aureus; Screening procedure; Sensitization, Immunologic; Sensitization, Immunological; Severities; Shellfish; Shellfish - dietary; Shock, Anaphylactic; Site; Skin; Social Interaction; Staphylococcus aureus; Stomach; T1 diabetes; T1D; T1DM; Testing; Therapeutic; Therapeutic Epinephrine; Therapeutic Intervention; Toxin; Type 1 diabetes; United States; Visit; adult human (21+); allergic dermatitis; allergic eczema; allergic to peanuts; antigen challenge; bsAb; children; disease/disorder; egg; food allergen; gastric; gene product; health care expenditure; host response; immunogen; immunoresponse; improved; innovate; innovation; innovative; insulin dependent diabetes; intervention therapy; intraoral drug delivery; juvenile diabetes; juvenile diabetes mellitus; ketosis prone diabetes; living system; model organism; novel; peanut allergy; pediatric; prevent; preventing; psoriasiform; psoriatic; psoriatiform; resistant; response; screening; screenings; sensitizing antigen; tool; treatment response; trial regimen; trial treatment; type I diabetes; youngster
Project start date: 2008-04-01
Project end date: 2010-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2010
PFA/PA: PA-07-336
5R21AI078525-02 (2009): $188750