Bee Venom-specific IgE Research Articles

Safety of 100\xa0\xb5g venom immunotherapy rush protocols in children compared to adults

BackgroundThere is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls.Methods72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7–17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions.ResultsCompared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9% vs 2.5%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04–4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25–5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg.ConclusionsThe higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.

Immune and clinical response to honeybee venom in beekeepers.

The aim of the study was to assess immune response to honeybee venom in relation to the degree of exposure, time after a sting and clinical symptoms. Fifty-four volunteers were divided into 2 groups: beekeepers and a control group. The serum levels of total IgE (tIgE), bee venom-specific IgE (venom sIgE), phospholipase A2-specific IgE (phospholipase A2 sIgE), tryptase and venom-specific IgG4 (venom sIgG4) were determined. In beekeepers, diagnostic tests were performed within 3 hours following a sting and were repeated after a minimum of 6 weeks from the last sting. In individuals from the control group, the tests were performed only once, without a sting. The tests showed significant differences in venom sIgE (beekeepers' median = 0.34 kUA/l, control group median = 0.29 kUA/l), baseline serum tryptase (beekeepers' median = 4.25 µg/l, control group median = 2.74 µg/l) and sIgG4 (beekeepers' median = 21.2 mgA/l, control group median = 0.14 mgA/l), confirming higher levels of the tested substances in the beekeepers than in the control group. A significant positive correlation was observed between phospholipase A2 sIgE concentration and severity of clinical symptoms after a sting in the group of beekeepers. It was also demonstrated that the clinical symptoms after a sting became less severe with increasing age of the beekeepers. The differences in the immune response to a bee sting between the beekeepers and individuals not exposed to bees were probably due to the high exposure of the beekeepers to honeybee venom allergens. This may suggest a different approach to the bee venom allergy diagnostic tests in this occupational group.

Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings

The aim of this study was to analyze the influence of total serum IgE and other potential risk factors on severity of systemic allergic Hymenoptera sting reactions. In a retrospective analysis of one thousand and two patients referred for insect allergy over 5 years, 865 reported systemic allergic sting reactions, most often by honey bees and wasps. In 758, total IgE, venom-specific IgE, and baseline tryptase levels were available and analyzed together with atopy state, age, and sex in relation to severity of sting reactions according to H. L. Mueller. In a binary logistic regression model considering, besides IgE, also other risk factors for severity, an influence of total and specific IgE on severity of systemic allergic sting reactions could not be shown, while high severity of systemic allergic sting reactions was significantly more often reported in patients with a baseline tryptase of ≥11.4 μg/l (P < 0.0001) and higher age (P = 0.026). In a bivariate analysis, however, in patients with grade IV reactions total IgE (P = 0.003) and honey bee venom-specific IgE (P = 0.001) were significantly lower than in lower severity grades. Bee venom-specific mean IgE rank was significantly higher in bee than in Vespula venom allergic patients (P = 0.0001). Connection of high severity sting reactions with lower IgE is mainly because of older age, which is associated with lower total IgE, and moreover with cardiovascular disease and elevated baseline serum tryptase, which are both risk factors for severe reactions.

Bee venom allergy in beekeepers and their family members

To analyze prevalence of allergic sting reactions, including the clinical and diagnostic features as well as management options in a population heavily exposed to honeybee stings such as beekeepers and their family members. The higher sting frequency is associated with an increased prevalence of allergic sting reactions. Major risk factors for allergic sting reactions in beekeepers are: fewer than 10 annual stings, an atopic constitution and symptoms of upper respiratory allergy during work in the beehive. Bee venom allergic beekeepers have higher levels of bee venom-specific IgG but lower skin sensitivity and bee venom-specific IgE than normally exposed bee venom allergic patients. Safety of bee venom immunotherapy is higher in beekeepers than in allergic controls, while efficacy of this treatment is similar in both groups. Beekeepers and their family members are at an increased risk of severe sting anaphylaxis and therefore need especially careful instruction with regard to avoidance of re-exposure, emergency treatment and specific immunotherapy with bee venom.

Risk assessment in determining systemic reactivity to honeybee stings in beekeepers.

The use of laboratory tests as a reliable method for risk assessment in determining the systemic reactivity of beekeepers to honeybee stings has proven unsatisfactory. This study was conducted to evaluate the usefulness of a structured questionnaire as a supplement to bee venom-specific IgE data in the prediction of systemic sting reactions of 78 beekeepers to honeybee stings. Participants in previous studies completed a questionnaire concerning potential risk factors of systemic sting reactions. Serum bee venom IgE was measured by CAP-RAST. Skin prick tests were performed with standardized bee venom extracts prior to the beekeeping season. Venom challenges were performed using unintentional field stings. A new questionnaire concerning sting reactions during the recent beekeeping season was sent to the beekeepers after it had ended. A multiple logistic regression analysis was done to evaluate the influence of potential risk factors upon systemic bee sting reactions. Four variables were significant. The pre-season presence of serum bee venom-specific IgE at concentrations exceeding 1.0 kU/L increased the risk of systemic reactions 12-fold. The risk was 10-fold if nasal or respiratory symptoms had occurred while working at hives. When the years spent in beekeeping were fewer than eight the risk of systemic sting reaction was 9-fold, any previous systemic reaction increased the risk 8-fold. The use of more detailed patient histories in combination with laboratory tests may markedly improve the reliability of risk assessment.

Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization *

Hyposensitization with been venom leads to full protection in most, but not all patients with IgE-mediated systemic reactions to bee stings. To determine the relationship of clinical reactivity to the release of mediators and to changes of antibody concentrations in the peripheral circulation at a bee sting challenge test. Blood was sampled before (1 min) and at 15, 60 and 180 min after a sting challenge from 19 patients on hyposensitization. Of these six still reacted and 13 were protected. Histamine, mast cell tryptase, bee venom-specific IgE and IgG in the serum, and histamine release from peripheral blood leucocytes (PBL) upon exposure to bee venom were determined. Tryptase above the detection level was found only at 15 (60) min in 4/6 (1/6) patients who reacted. After the sting challenge there was a significant increase of the histamine levels in patients who reacted at 15 min (P < 0.05) and in patients who did react at 60 and 180 min (P < 0.01). The total histamine content of PBL was significantly decreased after 15 and 60 min in patients who reacted (P < 0.01) and in those that did not (P < 0.05). Bee venom-induced histamine release was significantly reduced in patients reacting and those that did not at 15 min (P < 0.05), and was significantly decreased in reactors also at 60 and 180 min (P < 0.05/0.01). Specific IgG antibodies showed a minor decrease (P < 0.05) after the sting challenge in both groups, whereas specific IgE did not change significantly. These results indicate that bee venom anaphylaxis is associated with the release of mediators from both mast cells as well as basophils. Successful hyposensitization does not induce a state of immunological non-reactivity, but rather alters the magnitude and the pattern of mediator release.

Clinical and immunologic survey in beekeepers in relation to their sensitization

Beekeepers often present allergic symptoms and represent a natural and experimental model of anaphylaxis and specific immunotherapy. Two hundred BKs were investigated. Both allergic and nonallergic subjects were selected very carefully in terms of immunologic status and exposure to bee stings. They were surveyed by a questionnaire, the titration of total serum IgE, and bee venom-specific IgE and IgG. Skin tests to HBV were performed in 176 subjects. Skin test sensitivity to HBV and allergic symptoms were significantly ( p <0.0001) related to the estimated number of annual stings. BKs did not have allergy for more than 200 bee stings received in a year, and skin tests were negative in all cases. Many subjects who received between 50 and 200 annual stings had positive skin tests, and 9% of them had a systemic allergic history. Systemic anaphylaxis was present in 20% of BKs who received between 25 to 50 annual stings, and in 45% of BKs who are stung less than 25 times a year. Specific IgE was present in 42% of BKs whatever the number of stings received, but the titer was lower when the number of stings increased. The presence of specific IgE in subjects who are stung numerous times and who do not present allergic symptoms at the time of the stings suggests that outbreaks of anaphylaxis may be possible in nonallergic BKs. Specific IgG titrated by the Pharmacia IgG-RAST was less than 150 U/ml in most allergic subjects and over this level in most nonallergic BKs. There is a significant ( p <0.01) difference between the levels of specific IgG in allergic and nonallergic BKs that suggest that a serum concentration of 150 U/ml should be reached during HSV immunotherapy. YJV allergy was finally sought in 176 BKs by means of a questionnaire and skin tests. It was observed that yellow jacket—venom allergy is not uncommon and is more frequent than expected.

Clinical and immunological surveys in bee keepers.

Two hundred and fifty bee keepers in the South of France, working seasonally, were clinically investigated by means of a questionnaire. Forty-three per cent had presented anaphylactic symptoms and 7.0% toxic reactions when stung by bees. The personal atopic history was found to be significantly (P less than 0.01) elevated in bee keepers who experienced anaphylaxis. Total serum IgE and been venom-specific IgE were titrated in 100 subjects. Total serum IgE was significantly elevated in allergic bee keepers (P = 0.02). Although bee venom-specific IgE were significantly (P less than 0.01) higher in allergic bee keepers this parameter cannot discriminate between allergic and non-allergic bee keepers owing to a considerable overlap. Bee venom-specific IgG was assayed in seventy subjects. Their level was significantly (P less than 0.001) higher in allergic and non-allergic bee keepers as compared with non-allergic blood donors and non-bee-keeping allergic patients. In both bee keeper groups there was no difference in bee venom-specific IgG titres.

Insect venom allergy: a prospective case study showing lack of correlation between immunologic reactivity and clinical sensitivity

This case report demonstrates the lack of correlation between clinical sensitivity to insect venoms and immunologic reactivity as indicated by the presence of venom-specific IgE. A 20-yr-old venom collector was monitored over a 3-yr period with measurements of venom-specific IgE (skin test and RAST) and venom-specific IgG. In the first year of venom collection, multiple stings were tolerated with no reaction. In the second season, she had an anaphylactic reaction after a yellow jacket sting. Subsequently, there was a rising titer of serum yellow jacket and bee venom-specific IgE and positive skin-test reactions. In the third season, yellow jacket, hornet, and bee venom skin tests remained positive and serum IgE antibody titers remained elevated. Stings from all three insects were tolerated with no reaction. Throughout the 3-yr course, serum venom-specific IgG remained low and unchanged. The factors other than IgE-modulating clinical anaphylaxis, perhaps responsible for this clinical and immunologic dichotomy, are unknown. These observations add a further complication to the choice of patients for venom immunotherapy.

Clinical application of measurements of serum levels of bee venom-specific IgE and IgG

Bee venom-specific IgE and IgG antibodies were measured in the serum of beekeepers, bee-allergic persons, and normal persons infrequently stung without adverse effects. Beekeepers, who are stung frequently and relatively “immune” to bee stings, are characterized by high serum levels of IgG- and low serum levels of IgE-specific antibodies. Bee-allergic individuals have high titers of bee venom-specific IgE and generally low titers of bee venom-specific IgG. Following a bee sting, allergic individuals develop a rising titer of IgE antibodies, accompanied occasionally by a rise in IgG antibodies. Therapy with whole bee body extracts fail to effect IgE or IgG antibody titers. During the course of venom immunotherapy IgG-specific antibodies are stimulated and IgE-specific antibodies continue to decline. These observations suggest that: (1) bee sting allergy is a function of bee venom-specific IgE; (2) bee sting immunity is a function of bee venom-specific IgG; and (3) bee venom is an appropriate therapeutic antigen.

Studies of the antigenicity and allergenicity of phospholipase A 2 of bee venom

The antigenic and allergenic properties of phospholipase A 2 (PLA 2) and whole bee venom were compared by measuring the IgG and IgE antibody responses in animals and man. Precipitating antibodies raised in rabbits and reaginic and other antibodies raised in mice reacted about equally with both bee venom and PLA. The majority of human sera containing bee venom-specific IgE also contained PLA-specific IgE, although in somewhat lower titers. Similarly, most human sera with significant amounts of total antibodies reacting with bee venom also had antibodies reacting with PLA. Histamine and SRS-a release from leukocytes of sensitive patients followed challenge with whole bee venom and PLA in the majority of instances. However, mediator release from several patients' cells was obtained with bee venom only. These studies suggest that although PLA is a major allergen and antigen in bee venom, significant exceptions in patients' reactivity may limit its potential diagnostic and therapeutic usefulness.