Dialyzed venom skin tests for identifying yellow jacket-allergic patients not detected using standard venom.

Background: The chance of a nonspecific intradermal skin test response at venom concentrations greater than 1.0 microg/mL limits the diagnostic range and can interfere with the diagnosis of some affected patients.

Objective: To compare the diagnostic ranges and clinical detection rates of skin tests using dialyzed yellow jacket venom (DYJV) and undialyzed YJV (UYJV), particularly in patients who have had negative venom skin test results.

Clinical and entomological factors influence the outcome of sting challenge studies.

Background: The reported frequency of systemic reactions to challenge sting varies greatly.

Objective: To evaluate the interaction of clinical and entomological factors that determine the outcome of a challenge sting.

Methods: Patients allergic to yellow jacket were stung and monitored for systemic reaction.

Outcomes of allergy to insect stings in children, with and without venom immunotherapy.

Background: Children are thought to "outgrow" the allergy to insect stings, but there are no reports documenting the natural history of this reaction. We studied the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated.

Methods: Between 1978 and 1985, we diagnosed allergic reaction to insect stings in 1033 children, of whom 356 received venom immunotherapy.

Allergic potency of recombinant Fel d 1 is reduced by low concentrations of chlorine bleach.

Background: Sodium hypochlorite (NaOCl), the primary component of household bleach, has been shown to alter the purified mouse allergen Mus m 1, such that antibody recognition, or immunogenicity, is lost. Results of initial experiments suggest that antibody recognition is lost at lower concentrations of NaOCl than those required to fragment Mus m 1.

Objective: We sought to determine whether NaOCl had similar effects on recombinant (r)Fel d 1 and whether the loss of antibody recognition correlated with the loss of biologic activity, as measured with a basophil histamine release assay.

Case report of venom immunotherapy for a patient with large local reactions.

Background: Inadvertent Hymenoptera stings reportedly elicit large local reactions in up to 17% of the general population. Current practice parameters do not recommend venom immunotherapy (IT) for these cases.

Objective: The goal of this case study was to investigate the clinical and immunologic consequences of venom IT in a newly sensitized individual with large local reactions using an intentional sting challenge before and after treatment to document changes in reaction severity.

Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy.

Background: Recent studies have demonstrated that bacterially derived immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate immune system and promote the development of T(H)1 cells. Promotion of T(H)1 immunity by means of immunotherapy in allergic patients has led to the alleviation of symptoms that result from allergen-specific T(H)2 responses.

Objective: Our purpose was to investigate whether the T(H)1-enhancing properties of ISSs could be used to alter the T(H)2-dominated immune response of allergic PBMCs in vitro.

Insect sting allergy with negative venom skin test responses.

Background: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients with negative skin test responses who have had severe reactions to subsequent stings.

Objective: Our aim is to increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings.

Recombinant allergens with reduced allergenicity but retaining immunogenicity of the natural allergens: hybrids of yellow jacket and paper wasp venom allergen antigen 5s.

The homologous venom allergen Ag 5s from the yellow jacket (Vespula vulgaris) and paper wasp (Polistes annularis) have 59% sequence identity of their respective 204 and 205 amino acid residues, and they have low degrees of antigenic cross-reactivity in insect allergic patients and in animal models. Hybrids containing different segments of these two vespid Ag 5s were expressed in yeast. Circular dichroism spectroscopy suggests the hybrids to have the secondary structure of natural Ag 5.

Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1 enhances its immunogenicity and reduces its allergenicity.

Background: Allergen immunotherapy is inconvenient and associated with the risk of anaphylaxis. Efforts to improve the safety of immunotherapy by means of chemical modification of allergens have not been successful because it greatly reduced their antigenicity. Recently, immunostimulatory DNA sequences (ISS or CpG motifs) have been shown to act as strong T(H)1 response-inducing adjuvants.

Survey of patients after discontinuing venom immunotherapy.

Background: Venom immunotherapy rapidly reduces the risk of a systemic sting reaction in adults from 30% to 70% to less than 2%. When venom immunotherapy is stopped after 5 years or longer, the risk of a systemic sting reaction is 5% to 15% during the first few years after stopping treatment. It is uncertain whether systemic sting reactions will occur more than 5 years after discontinuing venom immunotherapy and whether treatment can be safely stopped in some patients after less than 5 years.

Relationship between histamine and physiological changes during the early response to nasal antigen provocation.

To investigate the temporal relationships of mediator release and physiological changes during the early response to allergen, we challenged allergic individuals intranasally with antigen and followed their responses. This was done by using small filter paper disks to challenge one nostril and collect secretions from both the challenged and the contralateral nostril, thus enabling us to evaluate the nasonasal reflex. There was a significant increase in sneezing after allergen challenge that peaked within 2 min and returned to baseline.

Daily variations of serum diamine oxidase and the influence of H1 and H2 blockers: a critical approach to routine diamine oxidase assessment.

Objective And Design: Histamine in food has been shown to induce intolerance reactions mimicking food allergy. These reactions seem to be due to impaired histamine metabolism caused by reduced diamine oxidase activity. To validate routine serum diamine oxidase assessment, daily variations of diamine oxidase were evaluated.

Co-regulation of antigen-specific T lymphocyte responses by type I and type II cyclic AMP-dependent protein kinases (cAK).

While a differential sensitivity to cyclic AMP (cAMP)-mediated signaling between Th1 and Th2 cells has been hypothesized, differential activity of downstream signaling through cAMP-dependent protein kinase (cAK) isoforms remains unexplored. We herein report the effects of type 1- and type 2-specific cAK agonists and antagonists on proliferative responses and cytokine generation from ragweed-driven peripheral blood mononuclear cells (PBMCs) and Amb a 1-specific Th1 and Th2 clones. Rp-8-Cl- and Rp-8-CPT-cAMP were utilized as single agent antagonists of cAKI and cAKII, respectively; 8-AHA-cAMP, with and without 8-PIP-cAMP, and 8-CPT-cAMP, with and without 6-Bnz-cAMP, were used as synergistic agonist pairs specific for the cAKI and cAKII, respectively.

Intranasal salmeterol inhibits allergen-induced vascular permeability but not mast cell activation or cellular infiltration.

Background: Salmeterol is a long-acting beta2-adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non-bronchodilator actions of salmeterol may contribute to its efficacy.

Objective: To further evaluate the potential non-bronchodilator actions of salmeterol in vivo, using a model of nasal challenge with allergen.

IL-4 secretion and histamine release by human basophils are differentially regulated by protein kinase C activation.

The role of protein kinase C (PKC) activation was investigated in the secretion of interleukin-4 (IL-4) protein by human basophils. Phorbol myristate acetate (PMA) induced little to no detectable IL-4 protein in culture supernatants, despite being a potent secretagogue of histamine release by basophils. In fact, the secretion of IL-4 by basophils stimulated with ionomycin alone was down-regulated (30-70%) with the simultaneous addition of PMA.

Effects of peptide therapy on ex vivo T-cell responses.

Background: Peptide therapy targets T cells directly with short peptides containing multiple T-cell receptor epitopes. Murine studies suggest T-cell anergy as the mechanism of action; however, changes in T-cell cytokine profiles may be more relevant in human beings.

Objective: We sought to study the effects of peptide therapy on ex vivo antigen-specific T-cell responses.

Discontinuing venom immunotherapy: extended observations.

Background: Our studies of discontinuing venom immunotherapy after at least 5 years have led to the conclusion that the residual risk of a systemic reaction to a sting was in the range of 5% to 10% in adults, and no severe or life-threatening reaction occurred with 270 challenge stings in 74 patients after 1 to 5 years without venom immunotherapy.

Objective: The objective of this study was to extend our observation of patients who discontinue venom immunotherapy over 5 to 10 years and to determine which patients are at higher risk for a reaction.

Methods: Patients who discontinued venom immunotherapy were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the fate of venom sensitivity.

Differential regulation of IL-4 and IL-13 secretion by human basophils: their relationship to histamine release in mixed leukocyte cultures.

Human basophils are an important source of IL-4, a cytokine that is central to the pathogenesis of allergic inflammation. Recent reports have indicated that these cells also generate IL-13, which shares a number of biologic properties with IL-4. We found basophils to be the major source of IL-13 produced in mixed leukocyte cultures following 20-h activation with a variety of stimuli.

Natural history of Hymenoptera venom sensitivity in adults.

Background: Epidemiologic studies of Hymenoptera venom allergy in adults show a prevalence of positive venom skin test results, RASTs of 15% to 25%, or both, but most such individuals have had no systemic reactions to stings. The clinical significance and natural history of this apparently common sensitivity is uncertain.

Objective: We sought to determine the natural history of venom sensitization by observing the rate of decrease or increase in sensitivity in normal adults over 5 to 10 years.

SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: in vitro anti-inflammatory actions.

First-generation phosphodiesterase 4 (PDE4) inhibitors, such as rolipram, inhibit the activation of immune and inflammatory cells. The clinical use of these compounds is limited by gastrointestinal side effects, such as increased acid secretion and nausea. Consequently, the challenge has been to design novel PDE4 inhibitors that maintain the anti-inflammatory actions of rolipram while achieving an improved side effect profile.

Nasal provocation with allergen induces a secondary serum IgE antibody response.

The study of the IgE response to seasonal antigen exposure is limited by its occurrence once a year and by the variability of patient exposure to pollens. To overcome these problems, we investigated whether nasal challenge with antigen causes an increase in serum anti-ragweed IgE levels. We challenged individuals with ragweed allergy intranasally with nanogram quantities of ragweed antigen extract and measured their serum anti-ragweed IgE levels before and at weekly intervals after challenge.

Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses.

Corticosteroids are potent antiinflammatory agents that modulate human T-lymphocyte responses. Controversy remains as to their possible differential effects on Th1 and Th2 subsets. This study explores the kinetics and efficacy of these agents in human, antigen-driven peripheral blood mononuclear cells (PBMCs) and in nontransformed, antigen-specific Th1 and Th2 clones.

A double-blind study of the discontinuation of ragweed immunotherapy.

Background: Immunotherapy effectively treats the symptoms of allergic rhinitis and improves its pathophysiology. We studied whether the effects of immunotherapy on the early response to nasal challenge with antigen and seasonal symptoms persist after discontinuation.

Methods: Twenty subjects with ragweed allergy who were receiving immunotherapy and who had nasal challenges performed before initiation of treatment were selected.

Differential regulation of human, antigen-specific Th1 and Th2 responses by the B-7 homologues, CD80 and CD86.

A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD86) for promoting Th2 responses in the murine system has recently been suggested.