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Background: Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was to explore the immunological mechanism of anaphylaxis to PBV. Methods: PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods. Results: Five of the nine patients had a positive CD-sens to PBV which was completely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubating the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD-sens was completely or partially destroyed by heating at +56°C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%. Conclusion: Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reaction. Further studies are needed to characterize the postulated carrier.

To cite this article: Johansson SGO, Florvaag E, Oman H, Poulsen LK, Mertes PM, Harper NJN, Garvey LH, Gerth van Wijk R, Metso T, Irgens A, Dybendal T, Halsey J, Seneviratne SL, Guttormsen AB. National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study. Allergy 2010; 65: 498–502. Abstract Background: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased. Methods: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop® test (>0.35 kUA/l), collected in nine countries representing high and low PHO-consuming nations. Results: There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization. Conclusion: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

P>Background: This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma. Methods: The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV1 and a questionnaire. Results: Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower (P < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels. Conclusion: Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results. (Less)

The use of pine nuts, the seeds of Pinus pinea, is on the increasing in the modern Mediterranean diet. Little more than 20 cases of allergy to this tree nut have been published, and cross-reactivity with pine pollen, peanut and almond has already been reported. We describe the case of a young boy with several episodes of anaphylaxis after pine nut ingestion. Specific IgE to pine nut and Artemisia vulgaris was demonstrated by skin prick tests and in vitro determination of specific IgE, although no IgE to pine pollen or other nuts was detected. Immunoblotting of Artemisia vulgaris and pine nut revealed two matching diffuse bands, just below 14 kDa and 30 kDa. The ImmunoCAP inhibition assays showed complete inhibition of pine nut specific IgE after serum incubation with Artemisia vulgaris extract. As far as we know, this is the first reported case of documented cross-reactivity between pine nut and Artemisia vulgaris.

Background: Neuromuscular blocking agents (NMBAs) can cause anaphylaxis through immunoglobulin E (IgE) antibodies that bind quaternary ammonium ion epitopes. These epitopes are present in numerous common chemicals and drugs, exposure to which, theoretically, could be of importance in the development and maintenance of the IgE sensitization promoting allergic reactions. Pholcodine is one such drug, which in a recent pilot study was shown to induce a remarkable increase in serum IgE levels in two IgE-sensitized individuals. The present study explores the effect of pholcodine exposure on IgE in a population with previously diagnosed IgE-mediated anaphylaxis towards NMBAs. Methods: Seventeen patients were randomized to 1 week’s exposure with cough syrup containing either pholcodine or guaifenesin. The primary variables serum IgE and IgE antibodies towards pholcodine, morphine and suxamethonium were measured before and 4 and 8 weeks after start of exposure. Results: Patients exposed to pholcodine had a sharp rise in levels of IgE antibodies towards pholcodine, morphine and suxamethonium, the median proportional increases 4 weeks after exposure reaching 39.0, 38.6 and 93.0 times that of the base levels respectively. Median proportional increase of IgE was 19.0. No changes were observed in the guaifenesin group. Conclusion: Serum levels of IgE antibodies associated with allergy towards NMBAs increase significantly in sensitized patients after exposure to cough syrup containing pholcodine. Availability of pholcodine should be restricted by medical authorities because of the potential risk of future allergic reactions to muscle relaxants.

Background: Many clinical trials with omalizumab, Xolair, have been reported but the treatment period has always been short, i.e. < 12 months. After withdrawal, the clinical symptoms tend to return. A group of patients who stopped treatment after approx. 6 years allowed studies of the long-term effects of Xolair. Methods: The patient's cat or mite allergen sensitivity was quantitated as basophil allergen threshold sensitivity, CD-sens, and immunoglobulin E (IgE) and IgE- and IgG4-antibodies were determined before start and during treatment withdrawal. Asthma severity was evaluated from forced expiratory volume (FEV), peak expiratory flow (PEF) and a questionnaire. Results: At 6-14 months without Xolair 13 of the 18 cat and mite allergic asthmatics had either improved or remained the same as on treatment. Most of the patients were in a stable clinical condition reporting high quality of life, no increased nightly asthma attacks, no emergency visits as well as little or no increase in medication. The CD-sens to cat showed a peak 4 months after withdrawal but then decreased to levels below those of untreated patients with allergic asthma and at 12 months six of 14 had nonreactive basophils. Cat IgG4 antibody levels were higher than in cat allergics in general. Conclusion: Most of the patients 12-14 months had, after closing of 6-year Xolair treatment, a surprisingly mild asthma. Interestingly, and probably contributing to the clinical results, a downregulation of basophil, and presumably also mast cell, reactivity, was seen. (Less)

Background: Dosages of anti-immunoglobulin (Ig)E in treatment of allergic asthma is based on total IgE body pool assuming that IgE antibodies responsible for the disease are evenly distributed among patients. This assumption was evaluated. Methods: Median and quartile concentrations of IgE and IgE antibodies to cat and mite in 6461 sera submitted to an allergy laboratory during 2003–2005 were calculated and expressed in groups of different IgE levels. Results: Of 3872 (60%) samples from adults with a serum IgE level of 30–700 kU/l, 22.2% had IgE antibodies (≥0.35 kUA/l) to mite, 36.0% to cat and 8.1% to both. The relative concentration of IgE antibody of IgE decreased with increasing IgE, indicating a more specific response in patients with slightly elevated serum IgE. At a hypothetical serum IgE level of 10 kU/l, the threshold recommended for anti-IgE treatment, 25% of the originally mite- and/or cat-positive population in the

Background: A previous study showed a relation between pholcodine (PHO) consumption, prevalence of IgE-sensitization to PHO, morphine (MOR) and suxamethonium (SUX) and anaphylaxis to neuromuscular blocking agents (NMBA). The purpose of this pilot study was to explore the effect on IgE production, in IgE-sensitized and nonsensitized individuals, of exposure to cough syrup and environmental chemicals containing PHO, MOR and SUX related allergenic structures. Methods: Serum concentrations of IgE and IgE antibodies to PHO, MOR and SUX allergens measured by ImmunoCAPTM (Pharmacia Diagnostics, Uppsala, Sweden) were followed after intake of cough syrup, or exposure to confectionary and other household chemicals containing various amounts of substances cross-reacting with PHO, MOR and SUX. Results: Cough syrup containing PHO gave, in sensitized individuals, within 1–2 weeks, an increase of IgE of 60–105 times and of IgE antibodies to PHO, MOR and SUX in the order of 30–80 times. The tested confectionary did not have any similar stimulating effect but seemed to counteract the expected decrease of IgE. No effect was seen in nonsensitized individuals. The PHO stimulated IgE showed a nonspecific binding to ImmunoCAP with common allergens and glycine background ImmunoCAP that was up to 10-fold higher than that of monomeric myeloma-IgE at twice the concentration. Conclusions: It seems as cough syrups containing PHO have a most remarkable IgE boostering effect in persons IgE-sensitized to PHO, MOR and SUX related allergens. Household chemicals containing such allergenic epitopes seem capable of some, minor, stimulation.

Background: Predatory mites are used as biological pesticides worldwide for control of spider mites and other pests in greenhouses. The aim of this study was to evaluate the impact of occupational exposure to Phytoseiulus persimilis and Hypoaspis miles on IgE sensitization among a large group of Swedish greenhouse workers and to examine the relationship between exposure and allergic asthma and rhinoconjunctivitis. Methods: A total of 96 greenhouse workers from the southern part of Sweden, who were using the predatory mites for control of pests, were investigated with a questionnaire and a medical examination including lung function test. Blood samples were taken to test for allergen-specific IgE antibodies to Phytoseiulus persimilis and Hypoaspis miles as well as to Tetranychus urticae, Dermatophagoides pteronyssinus/farinae and Tyrophagus putrescentiae. Results: Seventeen of the 96 workers were positive in ImmunoCAP to predatory mites: 17 to P. persimilis (17.7%) and 14 to H. miles (14.6%). Subjects sensitized to predatory mites were significantly more often atopic (13/17), defined as a positive Phadiatop, than those who lacked IgE against these mite species (17/79) (P

Background/aims: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin. Methods: Patients (n‰109) with atopic dermatitis were treated for 30 days with a moisturiser in a randomised, parallel and double-blind fashion. Transepidermal water loss (TEWL) and skin capacitance were assessed instrumentally, and changes in the dryness of the skin were assessed by the dermatologist. Results: No difference in TEWL was found between glycerine treatment and its placebo, whereas a lower value was found in

The aim of this study was to establish whether there is a link between sensitisation to peanut and exposure to peanut oil in vitamin A and D preparations. Forty-one children with a positive in vivo or in vitro test towards peanut were included. Twenty-one children had consumed vitamins A and D in oil solution, 14 in water solution, and 6 both types. Refined and unrefined peanut oils were obtained and skin prick test extracts were prepared. None of the children exhibited a positive SPT in response to the refined peanut extract. In contrast, 15 children exhibited a positive SPT to the unrefined extract. There was no significant difference in the number of children reacting clinically to peanut exposure who had received vitamins A and D in oil-based or water-based formulations. However, children with clinical allergy to peanut and who had exclusively consumed vitamin A and D in peanut oil, exhibited a greater number of different allergic symptoms upon consumption of peanut compared with clinical allergic children who had consumed the vitamins in water solution or both types (p

Intestinal tight junction function is thought tobe of importance in the pathogenesis of variousdiseases. The regulation of uptake of macromolecules viathe tight junctions is largely unknown. Effects of luminal sodium caprate (10 mM), a dairyproduct constituent, and cytochalasin B (30 μM), werestudied in rat ileum in vitro in Ussing chambers. Bothagents caused a reversible fall in potential difference and increased [51Cr]EDTApermeability. In addition, sodium caprate inducedincreased permeability to polysucrose (15,000 daltons)and opening of the tight junctions as visualized bytransmission electron microscopy. Doseresponse patterns suggestedmainly dose-dependent differences between the agents.Confocal laser scanning microscopy suggestedparacellular permeation of polysucrose. Luminal sodiumcaprate, a food constituent, can increase tight junctionpermeability, allowing passage of macromolecules,without affecting epithelial viability. Increasedpermeability to mediumsized molecules does notnecessarily coincide with increased paracellular uptake ofproteinsized molecules.

Background: Patients immunoglobulin (Ig)E-sensitized to more than one allergen in their environment often have more symptoms than mono-sensitized individuals, which indicates that the allergens may have an additive effect. In order to study if such an effect could be detected on the inflammatory, cellular level, multisensitized basophils were challenged with various dose combinations of two relevant allergens. Methods: Basophils from patients IgE-sensitized to timothy/cat, birch/cat, timothy/mite and cat/mite were challenged with serial dilutions of different combinations of the two allergens. The basophil response was measured as CD63 expression analysed by flow cytometry. Results: The doses of each allergen in the pair had an additive effect resulting in a shift of the dose–response curve to higher CD63 percentages and higher CD-sens. Conclusions: If a patient has IgE antibodies and thus sensitized basophils to more than one allergen, to which he is simultaneously exposed, the additive effect should be considered. Even low concentrations of IgE antibodies could be of clinical relevance in such a situation.

The importance of maternal infections with Toxoplasma gondii, cytomegalovirus (CMV), Parvovirus B19, respiratory syncytial virus (RSV), and influenza A and B on fetal IgE synthesis was studied in 153 pregnant women. No case of specific IgM activity or viral DNA in cord blood, indicating a congenital infection, was found. From gestational week 15 to delivery, maternal IgG-Ab seroconversion to Parvovirus B19, RSV, influenza A, or influenza B occurred in 47 women. At delivery, serologic signs of past infection with T. gondii were observed in 29 (19%) women, and the corresponding figure for CMV was 117 (77%). The number of women with positive IgG seroconversion during pregnancy or positive IgG-Ab activity toward the studied infectious agents at delivery did not differ significantly among infants with an increased (> or = 1.3 kU/l; n = 51) or with an undetectable (< 0.1 kU/l; n = 102) cord-blood IgE level. These results show that genetic and other environmental factors probably have a greater influence on fetal IgE synthesis than do maternal infections during pregnancy.

Summary Background Evaluating in vivo and/or in vitro tests for ‘early’ prediction of childhood allergy is of interest in paediatric allergology. Objective To determine whether the measurement of Phadiatop Paediatric (PP) during early childhood could be used to predict the development of atopic disease during the first 5 years of life among infants with a family history of atopic disease. Methods Phadiatop Paediatric was evaluated in 134 infants. The analysis was performed at 6 months, at 18 months and at 5 years of age and the numbers of available serum samples were 61, 85 and 134, respectively. The potential capacity of the test to predict the development of atopic disease was studied by relating the result of the test, a positive or a negative score, to the cumulated incidence of atopic diseases from birth to 18 months of age and from birth to 5 years of age. Results Three of four children with a positive PP at 6 months of age developed clinical signs/symptoms of atopic disease before 18 months and all four before 5 years of age. The predictive value of a positive test at 18 months for symptoms before 5 years of age was 80% (12/15). If the diagnostic criterion, instead of clinical signs/symptoms of atopic disease, was at least one positive skin-prick test to major food or inhalant allergens, the predictive value of a positive PP-test at 18 months decreased to 53% (8/ 15). Conclusion Although the presence of circulating IgE antibodies, as detected by Phadiatop Paediatric, can predict the development of atopic diseases during childhood, the usefulness of the test is limited by its low sensitivity (22-47%).

Serum IgA and IgE levels were studied in the postnatal period in 21 infants having a paternal heredity of atopic disease. Three different sampling techniques were used, aspirated cord blood (CB), gravity-collected cord blood, and capillary collected blood at 4-5 days of age. Significant differences among the three sampling techniques were recorded for IgA (P < 0.01), but not for IgE. The IgA levels decreased from birth to 4-5 days of age in 90% (19/21 of infants (P < 0.01). The corresponding decrease in IgE levels was 20%. This postnatal difference in the frequency of decreasing/increasing IgA and IgE levels was significant (P < 0.05). An analysis of CB IgA to detect maternal contamination of CB was found to be of questionable value, since only 50% (2/4) of the cases with an elevated CB-IgA level could be considered contaminated. The results of this study further emphasize that aspiration of CB and capillary collection of blood at 4-5 days of age are the best sampling techniques to avoid contamination. The general finding that paternal heredity had no significant influence on infant IgE contrasts with the strong influence of maternal heredity. Further studies will show whether the explanation lies in genetic or transplacental factors, or in both kinds of factors.

We recently reported increased intestinal permeability to polysucrose (PS) 15000 in patients with Crohn's disease and in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We have now compared this new macromolecular marker (14,700 D) with the conventional markers, 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) (342 D) and 14C-mannitol (182 D), in healthy humans.Twenty healthy volunteers on four occasions ingested a solution containing PS 15000, 51Cr-EDTA, and 14C-mannitol, the test solution being, respectively, isoosmolar, hyperosmolar, isoosmolar followed by a standard meal, and isoosmolar after 1 week of NSAID treatment. Fractional urinary excretion of the substances was measured over 0-4 h, 4-8 h, and 8-12 h.The excretion of PS 15000 was, like that of 51Cr-EDTA but unlike that of 14C-mannitol, increased by NSAID pretreatment, little affected by hyperosmolar test solution, little correlated to urinary volume, and skew with regard to frequency distribution. Despite being nominally about 40 times lower, the excretion of PS 15000 was highly correlated to that of 51Cr-EDTA but not to that of 14C-mannitol. A standard meal reduced the test variability for all three probes.PS 15000 may be an alternative to 51Cr-EDTA as a small-intestinal permeability marker. Inclusion of a standard meal reduces test variability.

Objective: To examine whether synthetic polysucrose behaves as a transcellular or paracellular marker in patients with Crohn's disease and in healthy subjects. Design: Patients with Crohn's disease (n = 23) and age- and sex-matched healthy controls (n = 22) were given an oral dose of polysucrose with a mean molecular weight of about 15 kDa, administered with a standard meal. Methods: Intestinal permeability to polysucrose was estimated as urinary excretion of the compound measured by immunoassay during 0-4, 4-8 and 8-12 h. Results: Urinary excretion values for polysucrose in the controls had a non-symmetrical frequency distribution and were not correlated to urinary volume

Comparison was made of IgE and IgA levels in aspirated and gravity-collected cord blood (CB) from the umbilical vein and in capillary blood samples collected on the 4-5th day of life among 21 infants with atopic heredity. The IgA levels, but not the IgE levels, were significantly (p0.001) lower at days 4-5 of life than at delivery. Further, there were significantly (p0.05) more infants with decreasing IgA levels (20/21; 95%) than IgE levels (9/15; 60% of those with detectable IgE, i.e.,or = 0.125 kU/l). These observations, together with the highly significant correlation observed between IgE in aspirated CB samples and at 4-5 days of age, suggest active IgE synthesis during the prenatal and postnatal periods. Contamination of CB with maternal blood, defined as an increased CBIgA level (or = 14.1 micrograms/ml), was found in 3 (14%) CB samples, all of which were gravity-collected. Of 4 CB samples (gravity-collected) with elevated IgE (i.e.,or = 0.9 kU/l), 2 had suspected maternal contamination. Therefore, aspiration of CB or capillary collection at 4-5 days of age should be preferred for allergy prediction. If gravity collection is used, contamination should be investigated by determining IgA in all CB samples with IgE concentrations exceeding the cut-off point.

Some patients with allergic asthma treated with anti-IgE (Xolair) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens).In a double-blind placebo controlled trial 20 patients with a high (3.8%) and 18 with a low (1%) percentage of IgE antibodies to cat were given Xolair for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo.The CD-sens dropped significantly in both the high (P0.001) and low (P0.001) group on Xolair but did not change significantly after placebo. For Xolair-treated patients, at the end of the trial there was a highly significant (P0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative.The currently recommended doses of Xolair very efficiently eliminate IgE antibodies if the IgE antibody fraction is1% of total IgE but has not enough effect on allergen sensitivity if the fraction is3-4%. Further studies will show if increased doses of Xolair would help also these patients, who seem to represent about 1/3 of the patient population.

Allergen-specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long-term development of these diseases. Basophil allergen threshold sensitivity, CD-sens, which is a valuable complement to resource-demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen 'blocking activity'. Patients IgE-sensitized to timothy (n = 14) or birch (n = 19) pollen were started on conventional (8-16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD-sens, allergen binding activity (ABA) and serum IgG4- and IgE-antibody concentrations. CD-sens decreased during the early phase of ASIT-treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. CD-sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT. (Less)

The IgE levels and food-allergen-specific IgE- and IgG-antibodies (Ab) to ovalbumin (OA), ovomucoid (OVO) and beta-lactoglobulin (BLG) were determined up to 18 months of age in 163 infants born to women who were atopic. A high (HIGH group) or a low (REDUCED group) intake of hen's egg and cow's milk by the mother during the third trimester gave no significant differences in the concentrations of IgE or in IgE-Ab (OVO, BLG) and IgG-Ab (OA, OVO, BLG). Similarly, a prolongation of the abstention diet to the early lactation period did not influence the immune response. The IgG-Ab levels to all three food allergens decreased significantly (P less than 0.001) in both study groups between birth and 2 months of age, but then increased significantly (P less than 0.001) between 6 and 18 months of age. The presence in serum of IgE-Ab to OVO (greater than or equal to 0.15 PRU/ml) was associated with significantly higher IgG-Ab levels to OVO at 6 months (P less than 0.001) and at 18 months (P less than 0.05). Infants with positive skin-prick tests (SPT) to OA and OVO showed higher IgG-Ab levels at 6 and 18 months of age than did infants with negative SPT reactions to the two egg allergens. This indicates a relation between the IgE- and IgG-Ab response and it also suggests that some individuals are 'high responders' to both types of immunoglobulin isotypes while others are 'low responders'.

Background: The general understanding is that a blood sample for analysis of immunoglobulin (Ig) E antibodies to an allergen suspected to cause an anaphylaxis cannot be drawn until several weeks after the reaction. As this is most unpractical, the changes in IgE antibody levels during anaphylaxis were studied to evaluate the possibility of using samples drawn at the time of the reaction. Methods: Immunoglobulin E antibodies to suxamethonium were quantitated with ImmunoCAP before, during and after an anaphylactic reaction occurring during anaesthesia using neuromuscular blocking agents. Results: Serum IgE antibody concentrations against suxamethonium in blood samples collected up to 6 h after the reaction were not different from those in samples drawn before or days and weeks after the anaphylaxis. Conclusions: A serum sample intended to trace the drug involved in an IgE-mediated anaphylactic reaction can be drawn in direct relation to the reaction.

Background: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment. Methods: Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations. Results: There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE' (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy. Conclusions: CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information. (Less)

Background: Reactions after a blood transfusion could be allergic because of passive transfer of immunoglobulin E (IgE) antibodies from allergic donors. Aims of the study: To compare spectrum and prevalence of IgE antibodies in blood donors from Sweden and Norway. Methods: Using the ImmunoCAP method, serum samples from 1002 blood donors from Sweden and 500 from Norway were analysed for IgE antibodies to common inhalant and food allergens and allergens common in a hospital environment, such as penicilloyl G and latex. Results: As many as 23.6–27.3% of the donors had IgE antibodies to at least one of the 14 allergens tested. Of these 6.8–16.7% had extremely high concentrations, i.e. >35 kUA/l corresponding to 100 times the cut-off for a positive allergy test. Most donors were sensitized to pollens, dander and mite but several had very high levels of IgE antibodies to penicilloyl G, latex and peanut. The pattern of sensitizing allergens differed between Sweden and Norway. Conclusions: High serum levels of IgE antibodies to various allergens are common among blood donors and the degree of sensitization and spectrum of involved allergen varies between geographical regions. Present routines to identify IgE sensitized, potential risk, donors are not satisfactory; the sensitivity of selection procedures is about 25%.

In 1919 Ramirez reported (1) the first case of allergypassively transferred by a blood transfusion. The patientwas suffering from aplastic anemia and received bloodregularly, and usually without any reactions. However,this particular time, when riding a horse carriage inCentral Park a few days after the transfusion, the patientdeveloped asthma. Dr Ramirez noticed the significance ofthis special event and when tracing the blood donorfound that he was suffering from asthma due to horseallergy. Since this first description of transfer of anallergy, a few reports have followed. In 1941 Lovelessreported skin and mucosal sensitivity to ragweed aftertransfer of blood from ragweed allergic patients shown tohave circulating reagins to ragweed (2). The nonallergicrecipients became skin test positive for quite long times,in two of the five cases for 7 and 20 weeks, respectively. Acouple of other cases have also been reported (3, 4).The blood transfusion specialty has, through question-naires and by simple case histories taken by blood centerpersonnel, tried to identify and eliminate allergic, poten-tially dangerous blood donors. However, this procedurehas not been very successful; we found that 23% of thedonors were IgE-sensitized and had significant levels ofIgE antibodies to common allergens (5). Thus, the risk ofpassive sensitization by blood and plasma transfusion is areality. However, it also opens an opportunity to studyserological and inflammatory aspects of human IgE-sensitization in vivo.In the 1960s, before the discovery of the central role ofIgE (6) in allergic inflammation, extensive studies wereperformed on basophil granulocytes and their role inallergic reactions (7). Cells, sensitized in vivo or in vitrowith reagin, were challenged with allergen and thebasophil response was measured as histamine release. Inthe early 90s, it was reported that when the basophilsempty their histamine containing granulae a structure onthe granulae vesicle, CD63, becomes exposed on the cellsurface (8). Appearance of CD63 on the surface ofbasophils, measured with flow cytometry, is now anestablished procedure to detect allergen or anti-IgEtriggering of basophils, and the accessibility of thebasophil specific marker CD203c (9) has made it possibleto more easily identify basophils.The objective of this study was to transfuse definedamounts of IgE antibodies to an allergen, and to examinethe degree and duration of IgE-reactivity in the recipient,Background: To study the mechanisms of passive sensitization of patientsreceiving plasma containing IgE antibodies to a defined allergen.Methods: When required for medical reasons, regular donor plasma with IgEantibodies to timothy grass allergen (8–205 kU

Background: Anaphylactic reactions to a neuromuscular blocking agent (NMBA) is more than six times as common in Norway as in Sweden, probably due to differences in preoperative sensitization. The prevalence of IgE-sensitization to morphine (MOR) and suxamethonium (SUX) in comparable populations in Bergen, Norway, and Stockholm, Sweden, was studied and related to possible sensitizing agents. Methods: Three hundred sera of ‘allergics’ and 500 blood donors in Bergen and Stockholm were tested for IgE antibodies to MOR and SUX using Pharmacia Diagnostics ImmunoCAP 1 (Uppsala, Sweden) assay and the results compared to those of 65 patients from Bergen with documented anaphylaxis to NMBA. In addition, 84 different household chemicals were tested, by IgE antibody inhibition, for SUX and MOR. Results: In Norway 0.4% of blood donors, 3.7% of allergics and 38.5% of anaphylactics were IgE-sensitized to SUX, and 5.0, 10.0 and 66.7%, respectively, to MOR. No serum from Sweden was positive. The majority of those sensitized (69%) were women. Several household chemicals contained SUX and/or MOR activity, but the only difference between Norway and Sweden was cough mixtures containing pholcodine (PHO). IgE antibodies to PHO were present in 6.0% of blood donors from Norway and in no serum from Sweden. Of the anaphylactics, 65—68% were sensitized to MOR or PHO but only 39% to SUX. Conclusions: IgE-sensitization to SUX, MOR and PHO was detected in Norway but not in Sweden. One possible explanation is the unrestricted use of cough mixtures containing MOR derivatives in Norway.

Studies of the nasal permeation of small molecules (1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15,000 (approx. 14,700 Da), to predict the mucosal permeation of inhalational allergens. PS 15,000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.

The ability of Phadiatop Paediatric (PP), Phadiatop (P), mixed-food RAST (MF), and the combination of P and MF to identify children with atopic allergy was evaluated among 193 children who had a family history of atopic disease, and who had an average age of 5 years. If atopy is defined as the presence of at least one positive skin prick test (> or = 2+) to common food and/or inhalant allergens, P had a sensitivity of 86%, a specificity of 94%, and an efficacy of 92%. These figures were somewhat better than the results with PP. However, when P was combined with MF, the sensitivity increased to 89%, but at the expense of lowered specificity (83%) and efficacy (84%). If the tests were related only to clinical signs/symptoms of atopic disease, the sensitivity and efficacy were, at maximum, 63% and 81%, respectively. There was a discrepancy between the results of P and PP in 9% of the children. One explanation of this discrepancy may be that PP seems to be incapable of detecting children with respiratory allergies induced by pollens from birch and related trees. The results indicate that in 5-6-year-old children P should be preferred to PP and to the combination of P and MF for atopy screening, at least in places where birch pollen is a common allergen.

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.

The influence of the mother's consumption of cows' milk and hens' egg on the immune response (IgE, IgG) in the mother and foetus was studied in 165 pregnant women with atopical respiratory disease with an allergy to pollen and/or animal dander. The women were randomly allocated to four diets ranging from a diet free from hens' egg and cows' milk to a diet containing intake of one egg and one litre of milk daily during the third trimester. No significant differences in cord blood IgE levels were noted in spite of differences in maternal diet, and no specific IgE antibodies to ovalbumin, ovomucoid and betalatoglobulin were found in the cord blood. The mother's IgG antibody concentrations to ovalbumin, ovomucoid and betalactoglobulin were influenced by her diet, but cord blood IgG antibody levels to the selected food allergens were unaffected. The data presented on the IgE and IgG antibody levels to ovalbumin, ovomucoid and betalactoglobulin in cord blood suggest that changes in maternal diet during the last trimester of pregnancy in order to prevent atopic sensitization in utero are less likely to affect the foetus than previously supposed.