IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY

点击翻译按钮获取中文摘要

DESCRIPTION (Adapted from Investigator's abstract): Over the last two decades this grant has supported studies showing that the then current therapy for insect allergy, whole body extracts, was not effective but that venom immunotherapy was effective. Venom immunotherapy became accepted in the United States (US) and worldwide. In the US, all adult patients with a history of anaphylaxis on insect sting and a positive venom skin test are treated. Recently, investigators in Holland found that if they sting challenge history positive, skin test positive patients, more than 70 percent have no reaction and, they contend, need no therapy. US studies found fewer non-reactors on re-sting. Neither the US nor the Dutch investigators have developed diagnostic parameters to predict which patients will or will not react on stings. The current application is based on the hypothesis that the Dutch study is, in part, correct and that it is unnecessary to treat as many patients as we do now. The investigators will repeat their work and address a flaw in that study - whether a single sting predicts the reaction to subsequent stings. It is known that in the early years of immunotherapy, IgG anti-venom antibodies correlate with clinical protection. It is hypothesized that this is an association, but not a causal one, and that clinical protection results from some other aspect of immunization. Using Fel d 1 peptides to immunize cat allergic individuals leads to a lesser immediate allergic response on exposure to cats. The investigators will immunize patients with peptides from antigen 5. Standard immunotherapy with venom leads to significant side-effects: approximately 50 percent of those treated have reactions ranging from a large local response to systemic anaphylaxis. Peptide immunotherapy does not cause immediate reactions, but in about 50 percent of patients, there is a late "anaphylactic-like" response, significantly milder in severity than the reactions to the allergen. The investigators hypothesize that these reactions are due to a HRF-like cytokine or one with direct anaphylactogenic properties. They have developed a protocol to ascertain the nature of this response. Finally, the major goal of these studies is to use the stings of more than 200 patients to develop parameters that predict which individuals will have a reaction to a sting. While this has not been accomplished before, this was due to stinging few unprotected individuals and the measurement of a limited number of parameters. It is now planned to study not only immunoglobulin levels but inflammatory cell activation, cytokine production, blood and urine histamine levels, and plasma tryptase and fibrinogen levels.