Evaluation of Hymenoptera hypersensitivity among forest administration workers

We used a questionnaire about Hymenoptera hypersensitivity to investigate 2546 forest administration workers in Nagano prefecture. The results were as follows. 1) Almost all of the workers (96.4%), including 528 (21.5%) hypersensitive workers, had been exposed to insect stings and 34 (1.4%) had lost consciousness as a result (i.e. anaphylactic shock). 2) Many of the workers had been stung by yellow jackets or wasps. 3) Their clinical symptoms were more severe when they were stung on the head or neck. 4) The rate of hypersensitive workers increased with the number of times they had been stung (p less than 0.05) and tended to increase with age. 5) The rate of atopy was higher among the hypersensitive workers than the non-hypersensitive workers (p less than 0.01), but those who lost consciousness did not necessarily have a high rate of atopy.     

Reproducibility of skin testing and serum venom specific IgE in Hymenoptera venom allergy.

BACKGROUND: The decision regarding an immunotherapy regimen for venom-allergic patients is based on the results of skin testing and serum venom specific IgE measurements. However, their reliability has been questioned, and their reproducibility has not been examined. OBJECTIVE: To evaluate the reproducibility and reliability of the results of skin testing and serum venom specific IgE measurement in venom-allergic patients. METHODS: Patients with a systemic reaction after an insect sting were evaluated twice, 2 to 6 weeks apart, by intradermal skin tests and by determination of serum venom specific IgE to Hymenoptera venoms. RESULTS: Thirty-five patients were evaluated 1 to 168 months (mean, 23 months) after the sting reaction. Reproducibility of skin test results for all venoms at the 2 sessions was found in 23 patients (66%). Reproducibility of venom specific IgE results for all venoms was found in 16 (59%) of 27 patients from whom 2 blood samples were available for evaluation. Concordance between skin test and venom specific IgE results for all venoms was found in 30 (51%) of 59 samples available for evaluation. CONCLUSIONS: The reproducibility of venom skin test and serum venom specific IgE results is relatively poor. It is common practice for therapeutic decisions regarding venom immunotherapy to be based on a single diagnostic evaluation. Consequently, many patients are either overtreated or undertreated. Better diagnostic methods are required in venom allergy.     

The predictive value of total serum IgE for a positive allergen specific IgE result

BACKGROUND: Measurement of total serum IgE and allergen specific IgE is often requested to assess possible allergy. As public awareness increases, so do requests for allergy assessment; unless there is a clear "allergen suspect" in the history, several allergen specific IgE requests may be made. This increases the likelihood of detecting borderline increases in allergen specific IgE of uncertain relevance, and has important cost implications for the service. AIMS: To provide an evidence base for this observation. METHODS: In this retrospective observational study, results from 301 patients under 16 years of age from whom blood was taken for "allergy testing" from March 2001 to February 2003 were studied. RESULTS: Allergen specific IgE testing in children with low total serum IgE concentrations (<10 IU/litre) yielded very few positive results (three of 73 children), except in those being investigated for an acute reaction to a single food; when IgE was 11-20 kU/litre, 13 of 73 children had positive allergen specific IgE; in the 21-40 kU/litre IgE group, 16 of 74 children had positive allergen specific IgE and in the 41-80 kU/litre group, 22 of 81 had positive allergen specific IgE. CONCLUSIONS: Allergen specific IgE testing in children with low IgE concentrations (<10 kU/litre) produces few positive results in patients with non-specific symptoms. Laboratories should perform allergy testing for specific allergens regardless of total IgE concentration only when there are convincing clinical reasons to do so, and should not proceed with this if the total IgE is <10 kU/litre and the presenting symptoms are non-specific.     

Evaluation of Hymenoptera hypersensitivity including large local reactions among forest administration workers in Gunma prefecture

We used a questionnaire to investigate Hymenoptera hypersensitivity in 715 forest administration workers in Gunma prefecture and measured venom specific IgE antibodies in those who had exhibited large local reactions (LLR). The results were as follows. 1) Almost all, i.e. 660 (92.3%), of the workers, including 156 (23.6%) hypersensitive workers, had been exposed to insect stings and 241 (36.5%) had experienced LLR. 2) Among the hypersensitive workers, 68.9% exhibited systemic reactions after having been stung no more than ten times and 18.2% experienced systemic reactions when they were stung for the first time. 3) About 60% of the hypersensitive workers had been stung on only one site when they exhibited systemic reactions. 4) An evaluation of venom specific IgE titer for the workers who experienced LLR revealed a relatively high rate of RAST positive results to yellow jackets (39.3%) and wasps (36.9%).     

Evaluation of decline in serum venom-specific IgE as a criterion for stopping venom immunotherapy

During a 7-year period, venom immunotherapy has been stopped in 57 patients because of a fall in IgE antibody titers to insignificant levels (RAST less than 10% STD). All patients had a history of venom anaphylaxis and elevated venom-specific IgE before therapy. Maintenance doses of 50 micrograms were administered every 4 to 6 weeks; 30 patients received yellow jacket venom, and 16 patients received honeybee venom only. Therapy was stopped after treatment from 1 to 8 years (mean 2.8 years). Repeat skin tests demonstrated an average two-log decrease in sensitivity; 35 of 55 tests remained positive at venom concentrations of less than or equal to 0.1 micrograms/ml. There were 55 re-stings in 24 patients, occurring from 3 months to 5 years after cessation of therapy, resulting in three systemic reactions. One patient, previously treated with bee venom, reacted to a yellow jacket sting. These re-sting reactors also had tolerated several other stings after therapy was stopped. Thus, the two actual reactions represent a "failure" rate of 8% per patient and 4% per sting, compared to reaction rates of 27% and 17% in patients who stopped therapy without physician advice. These data suggest that this criterion may be reliable for stopping therapy. However, subsequent tolerated re-stings may require continued patient evaluation.     

Increased total serum IgE in alcoholics

Total serum IgE concentrations were measured in 106 male alcoholics with current alcohol abstinence of varying duration. The influence of smoking habits and clinical atopy on IgE levels was considered. The majority (91%) of the alcoholics were smokers and 26% suffered from possible clinical atopy. The geometric mean IgE in non-atopic, smoking alcoholics was 42 kU/l and significantly higher than the mean IgE level, 19 kU/l, in age-matched, smoking, non-atopic male participants in a general health survey (p less than 0.001). The IgE levels declined with the length of the alcohol abstinence period. Alcoholics, serially followed after a heavy drinking spree, showed a uniform pattern of declining IgE levels during a fortnight of abstinence (p less than 0.001). No link was noted between total IgE levels and the extent of liver affection as estimated by various serum variables (bilirubin, aminotransferases, gamma-GT, IgG, IgA and IgM) or galactose tolerance test. The increased IgE levels in alcoholics are suggested to reflect an influence of ethanol on T lymphocytes regulating the IgE synthesis. Such a proposed effect of ethanol on cellular immunity may contribute to certain organic alcohol diseases, but does not appear to influence the frequency of clinical atopy, being similar in our patient group and in the general population of the same geographic area.     

Cellular histamine release, specific and total serum IgE levels in hay fever patients and controls

The amount of histamine released from blood leucocytes by allergen, the amount of allergen required to release 50% histamine and the total IgE and IgE specific for Dactyits glomerata are compared in nine hay fever patients and five control individuals. The variation with time of total IgE. of specific IgE and of the percentage of histamine released at a fixed allergen concentration, corresponding to the cellular sensitivity, is shown for one control individual with positive in vitro and skin tests, but without clinical symptoms. For four patients with a low total IgE level the evolution of these parameters during a 1 year treatment period is presented.     

Effect of prolonged venom immunotherapy on serum venom-specific IgE and IgG

Serum venom-specific IgE and IgG were monitored in twenty-three patients receiving venom immunotherapy for more than 3 years. Two response patterns of IgE antibody were found. Following initiation of therapy, seven patients had a rise in serum venom-specific IgE, peaking at one year, then decreasing. Sixteen patients had a persistent fall in IgE antibody titres following initiation of therapy. At the end of 3 years, levels of serum venom-specific IgE in both groups were comparable. The presence of atopy may have influenced the rising IgE antibody response. Serum venom-specific IgG either rose or remained elevated if the pretreatment titres were high. After several years of therapy, there was generally a decrease in serum venom-specific IgG.     

Total serum IgE and specific IgE antibodies in children with bronchial asthma

Correlation between total serum IgE levels and RAST scores in a total of 342 asthmatic children were evaluated. The median and range of serum IgE were 1,050 IU/mL and 20 to 10,000 IU/mL respectively. Positive rates of RAST were highest for mites and house dust (87% to 91%) and lowest for milk, dogs, buckwheat, and eggs (2% to 8%). In general, patients with higher RAST scores had higher serum IgE (P less than .05, Mann-Whitney test). In individual cases, however, serum IgE levels did not significantly correlate with RAST scores and RAST was mandatory to estimate the levels of specific IgE antibodies.     

Development of specific IgE antibodies after repeated exposure to snake venom

A patient who had been working with snakes for many years developed urticarial lesions on contact with the venom of the poisonous rinkals (Haemachates haemachatus). More recently, the patient complained of generalized allergic reactions occurring within minutes of exposure to the venom. The patient's serum, but not control sera, contained IgE antibodies that reacted with the specific snake venom in an ELISA and was demonstrated to associate with a 66 kd component of the venom with Western blotting. With an ELISA, the patient's serum was also demonstrated to contain IgG antibodies to the specific snake venom and to venom from three other snakes with which the patient had previously been in contact. The possibility of an acute allergic reaction should be considered in individuals continuously working with snakes or in individuals who have previously been bitten by snakes.     

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Background

Administration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.

Objective

To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy.

Methods

Based on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro.

Results

Intranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab.

Conclusion

Intranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.     

Preparation of rabbit anti-IgE for use in radioimmunoassays of total IgE and specific IgE antibodies

Detailed methodology for preparing and testing isolated rabbit anti-human IgE suitable for radioimmunoassays of total IgE and specific IgE antibodies is presented in a single article for the first time. A method for obtaining a product free of anti-idiotype antibodies is also described.IgE was isolated from E-myeloma serum (PS) by 40 and 50% saturated ammonium sulfate fractional precipitation, followed by DEAE Sephadex ion-exchange chromatography. The purified product was digested with papain, and the Fc fragments were separated from the Fab fragments by G-150 gel filtration and ion-exchange chromatography. Rabbits were immunized with IgE (Fc), and the antisera with the highest precipitin titers were pooled. A globulin fraction was prepared from the pooled antiserum by 50% saturated ammonium sulfate precipitation and the fraction was absorbed using an immunosorbent prepared from whole human serum having a very low IgE level and with immunosorbents prepared from D-myeloma protein and from IgE (Fab). Following absorption, the antibodies were demonstrated by micro-Ouchterlony technique to have no cross-reaction with IgG, IgA, IgM, IgD or any serum protein other than IgE. More than 200 mg of isolated anti-IgE (Fc) was prepared from antiserum globulin by consecutive affinity chromatography on columns of insolubilized IgE. Elution peaks appeared following the application of 0.1 M glycine—HCl, 1.0 M NaCl buffer, pH 2.5, as well as following a subsequent flush with 0.1 M phosphate, 1.0 M NaCl buffer, pH 7.4. The eluates were tested, pooled, radiolabelled with iodine-125 and demonstrated to be effective in RAST analyses. Antibodies to idiotypic determinants of the IgE molecule were eliminated by preparing the affinity chromatography column from a second E-myeloma protein (HL) rather than the E-myeloma protein (PS) used for immunization of the rabbits. Anti-IgE preparations which were free of anti-idiotype antibodies displayed less non-specific binding to IgD and IgG coated discs than preparations containing such antibodies.     

Relationship between total and allergen-specific IgE serum levels and presence of symptoms in farm workers sensitized to Tetranychus urticae

BACKGROUND: Clinical complaints in atopic subjects with asthma and rhinitis occur more frequently in the presence of high total and allergen-specific IgE serum levels. Here we report on the relationship between total and allergen-specific IgE serum levels and presence of symptoms in an unselected farmer population sensitized to Tetranychus urticae (TU). METHODS: Farmers were recruited as previously described. Total IgE and allergen-specific IgE were measured by immunoassay in TU-positive skin prick test (SPT) farmers (n = 58) and two control groups including Dermatophagoides pteronyssinus (Dp)-positive SPT subjects (n = 40) and non-atopic, TU-negative SPT healthy farmers (n = 25). RESULTS: Both TU+ and Dp+ subjects had significantly higher total IgE values (P < 0.001) than healthy non-atopic subjects. TU-specific IgE levels were significantly more elevated in symptomatic than non-symptomatic TU+ subjects (P = 0.028). Dp-specific IgE levels were higher in symptomatic than non-symptomatic Dp+ subjects (P = 0.003). Finally, total IgE levels were significantly higher in the symptomatic than non-symptomatic subgroups in both TU+ and Dp+ subjects (P < 0.0001 and P = 0.007, respectively). Logistic regression analysis showed that only total IgE concentrations were significant predictors of current symptoms in TU+ subjects. CONCLUSIONS: High total IgE and allergen-specific IgE levels are associated with symptoms in TU+ subjects. Definition of their predictive value requires further studies.     

Relation between total serum IgE levels and IgE antibody production in rats.

Five different rat strains were immunized with 100 microgram ovalbumin and 1 mg Al (OH)3. A good correlation was found between the total serum IgE level of a rat strain before immunization and the IgE antibody production. Good IgE antibody-producing strains had high total serum IgE levels and vice versa. A discordance between the evolution of the total serum IgE level after immunization and the changes in IgE antibody level was found in all strains.     

Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests

BACKGROUND: Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that these patients require additional tests to confirm the diagnosis. OBJECTIVE: To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test. METHODS: A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP-FEIA, in serum. If both tests proved negative, a controlled administration of the drug was then carried out. RESULTS: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P < 0.01). Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P < 0.001). CONCLUSION: These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.