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Background: Recent studies show that nsLTP sensitization is not limited to the Mediterranean basin and can present diverse clinical phenotypes. It remains challenging to predict clinical outcome when specific IgE antibodies (sIgE) to nsLTPs are present. This study compares both clinical and in vitro allergy characteristics but also diagnostic performance of a basophil activation test (BAT) and sIgG4 in nsLTP-sensitized patients from Antwerp (ANT, Belgium) and Barcelona (BCN, Spain)., Methods: Adult subjects with positive sIgE rPru p 3 and/or rMal d 3 ≥ 0.10 kU A /L (n = 182) and healthy controls (n = 37) were included. NsLTP-sensitized individuals were stratified according to clinical symptoms with peach/apple, respectively. BAT rPru p 3 and rMal d 3 were performed and sIgG4 antibodies to both components quantified., Results: In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 (0.001 µg/mL) can identify clinically relevant Mal d 3 sensitization (sensitivity of 60%-63% and a specificity of 75%-67%, respectively). In ANT, only the sIgE/total IgE rPru p 3 ratio shows added value (sensitivity 60% and specificity 83%). Finally, it appears that symptomatic patients in BCN are more sensitive to lower allergen concentrations compared to ANT. In addition, it was shown that ANT patients were more often sensitized to pollen and that specific pollen sources differed between regions., Conclusions: NsLTP-related allergy profiles and diagnostic performance differ significantly between regions and are component-specific, which makes extrapolation of data difficult to do. In addition, it seems that basophil sensitivity might show geographical differences. Additional research is needed to confirm these findings., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63-/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

IgE-mediated shellfish allergy constitutes an important cause of food-related adverse reactions. Shellfish are classified into mollusks and crustaceans, the latter belonging to the class of arthropoda. Among crustaceans, shrimps are the most predominant cause of allergic reactions and thus more extensively studied. Several major and minor allergens have been identified and cloned. Among them, invertebrate tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, and hemocyanin are the most relevant. This review summarizes our current knowledge about these allergens., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

IgE-mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life-threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross-allergies, mostly for plant foods. This clinical entity, designated as the 'cannabis-fruit/vegetable syndrome', might also imply cross-reactivity with tobacco, natural latex and plant-food-derived alcoholic beverages. Hitherto, these cross-allergies are predominantly reported in Europe and appear mainly to rely upon cross-reactivity between nonspecific lipid transfer proteins or thaumatin-like proteins present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross-allergies remains uncertain., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergy to atracurium is a rare condition with serious consequences of diagnostic error. However, correct diagnosis is not always straightforward. The aim of this study is to assess the utility of the basophil activation test (BAT) in atracurium sensitization and to investigate its role in identifying cross-reactivity between muscle relaxants., Methods: For validation, eight patients with perioperative anaphylaxis to atracurium and seven individuals experiencing perioperative anaphylaxis but not exposed to neuromuscular blocking agents (NMBA) were included. Furthermore, five other patient groups were included in the study, and all individuals exposed to different NMBA, either sensitized or not to the drug. Basophil activation with atracurium was analysed flow cytometrically., Results: ROC analyses between eight atracurium-sensitized patients and seven nonexposed controls allowed identification of 5% as the decision threshold for BAT positivity. For this cutoff, the BAT attained a sensitivity of 63%, specificity of 100%, positive predictive value of 100% and negative predictive value of 70%. Of the atracurium-exposed individuals with a negative atracurium skin test (ST), two individuals had a clear positive BAT. BAT atracurium was positive in one cisatracurium-sensitized patient and negative in all cisatracurium-exposed patients with a negative ST to cisatracurium. All rocuronium- and suxamethonium-sensitized patients displayed a negative BAT with atracurium., Conclusions: The BAT proves to be a useful diagnostic for atracurium-induced anaphylaxis and may be complementary to STs. The technique enables quick and simultaneous testing of potentially crossreactive NMBA and the identification of safe alternatives for future surgery., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error., Objective: To assess skin testing, quantification of specific IgE (sIgE) and flow-assisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy., Methods: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests., Results: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92-99%), 97% (CI 95%: 88-100%) and 83% (CI 95%: 74-89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86-99%), 75% (CI 95%: 67-75%) and 72% (CI 95%: 58-83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients., Conclusion: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT., (© 2011 John Wiley & Sons A/S.)

Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds. However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done. This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the diagnostic approach of this rare but potentially life-threatening complication. Apart from general principles about the diagnostic approach, history taking and importance of tryptase quantification, more specific confirmatory diagnostic procedures are organized on the basis of the major causes of perioperative anaphylactic reactions.

Physicians predominantly rely upon quantification of serum-specific immunoglobulin E (IgE) and/or skin test to confirm clinically suspected IgE-mediated allergy. However, for various reasons, identification of the offending allergen(s) and potentially cross-reactive structures is not always straightforward. Flow-assisted allergy diagnosis relies upon quantification of alterations in the expression of particular basophilic activation markers. Actually, upon challenge with a specific allergen, basophils not only secrete quantifiable bioactive mediators but also upregulate the expression of different markers which can be detected efficiently by flow cytometry using specific monoclonal antibodies. Currently, the technique has been applied in the investigation of IgE-mediated allergy caused by classical inhalant allergens, food, Hevea latex, hymenoptera venoms and drugs. It is also appreciated; the technique proves valuable in the diagnosis of non-IgE-mediated (anaphylactoid) reactions such drug hypersensitivity and the detection of autoantibodies in certain forms of chronic urticaria. This review will not address immunologic features, characteristics and general pitfalls of flow-assisted analysis of in vitro-activated basophils as summarized elsewhere. After a recapitulation of the principles and some specific technical issues of flow-assisted analysis of in vitro-activated basophils, we principally focus on the current clinical and research applications of the basophil activation tests. Personal experience of both research groups is provided, where appropriate. Finally, a viewpoint on how the field might evolve in the following years is provided.

Background: Diagnosis of anaphylaxis from neuromuscular blocking agents (NMBA) is not always straightforward., Objectives: To assess flow cytometric analysis of activated basophils (BAT) as a diagnostic instrument in anaphylaxis from rocuronium. To investigate whether the technique might help to identify cross-reactive and safe alternative compounds., Methods: For validation of the BAT, 14 patients with perioperative anaphylaxis demonstrating a positive skin test (ST) for rocuronium and eight individuals that tolerated rocuronium and a negative ST for this drug were enrolled. To confirm specificity of the BAT, five patients that tolerated atracurium or cisatracurium with a negative ST for rocuronium were tested. Basophil activation with rocuronium, vecuronium, atracurium, cisatracurium and suxamethonium was analysed flow cytometrically by labelling with anti-CD123/anti-HLADR/anti-CD63., Results: Sensitivity of BAT for rocuronium was 91.7% and specificity 100%. However, in two patients the BAT was lost as a diagnostic tool, as their cells were nonresponsive to positive control stimulation and allergen. Seven from the 12 responsive patients also demonstrated a clear basophilic activation for vecuronium. Moreover, according to ST and/or BAT cross-reactivity between rocuronium and vecuronium was suspected in 10/14 patients. Except one patient, all patients had negative BAT and ST investigations for atracurium and cisatracurium. Currently, five patients tolerated administration of cisatracurium. All control individuals demonstrated negative ST and BAT for all tested NMBA., Conclusions: The BAT constitutes a reliable instrument to diagnose anaphylaxis from rocuronium. The technique also allows quick and simultaneous testing of different potential cross-reactive NMBA and to tailor a safe alternative.

Background: IgE-dependent triggering of basophils not only elicits the release of different mediators but also the up-regulation of certain markers, e.g. CD63, which can be detected by flow cytometry. We intended to investigate if flow cytometric analysis of basophil activation could be a valuable tool in the diagnosis of latex allergy, and to evaluate if the basophil activation test (BAT) could be helpful in determining the clinical significance of a positive latex IgE in individuals with negative history and negative latex skin test. Additionally we aimed to determine the role of cross-reactive carbohydrate determinants (CCDs) in causing positive latex IgE without apparent clinical significance., Methods: Twelve healthy controls without a history of latex hypersensitivity with a negative latex IgE and skin test (group 1), 24 individuals without a history of latex hypersensitivity with a negative latex IgE and skin test but with other inhalant allergies (group 2), and 29 latex allergic patients with a compelling history of latex allergy with a positive latex IgE and prick test (group 3) were enrolled. The diagnostic performances of the BAT were further evaluated in 13 individuals with a history of latex allergy but with negative specific IgE and/or skin test (group 4). Twenty-four individuals with positive latex IgE without apparent clinical relevance, i.e. without history of latex hypersensitivity and negative latex skin tests, were also analyzed (group 5). The putative role of CCDs causing positive latex IgE results without apparent clinical significance was evaluated by quantification of IgE for bromelain., Results: According, to the receiver operating characteristics(ROC)-generated threshold value of 17% between latex allergic patients and the pooled group of nonlatex allergic individuals, the sensitivity and specificity of the basophil activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic patients without latex hypersensitivity and latex allergic patients the number of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with an evocative history of latex allergy but with negative latex IgE and/or skin test the BAT was positive in all 13 cases. Twenty of 24 individuals without apparent latex allergy but with positive latex IgE had a negative BAT. IgE for bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none of the 8 sera from group 4, but in 16/18 sera from group 5, respectively., Conclusion: Flow cytometric analysis of activated basophils seems a highly sensitive and specific tool for diagnosing latex allergy. In addition, the technique might help to determine the clinical relevance of positive IgE quantification in the absence of overt latex allergy. CCDs of natural rubber latex allergens were confirmed to mimic latex sensitization.

Human seminal plasma anaphylaxis (HSPA) is rare but may be life-threatening. The antigen or antigens involved in these reactions reside in a glycoprotein fraction of human seminal plasma (HSP). We report a woman who experienced HSPA. Literature on the subject is reviewed.

Soluble interleukin-2 receptor (sIL-2R), eosinophil cationic protein (ECP), the lymphoproliferative response to house-dust mite (HDM), adhesion to human umbilical vein endothelial cells (HUVEC), and lymphocyte membrane markers were studied in three groups of children: healthy children, asthmatic children without hyposensitization (HS), and asthmatic children with HS. HS was associated with significantly lower numbers of peripheral blood eosinophils (PBE) and lower sIL-2R serum levels and with a tendency to lower ECP serum levels and lymphoproliferative response to HDM. There were no changes in the T-lymphocyte phenotypic markers CD4 and CD8 among the three groups. The interleukin-2 receptor (IL-2R, CD25) on HDM-stimulated T lymphocytes increased over unstimulated T lymphocytes in the three groups. The CD25 expression was higher on HDM-stimulated lymphocytes in both asthmatic groups than in healthy children. Adhesion of lymphocytes on HUVEC increased significantly after HDM stimulation in asthmatic children without HS, whereas no change was observed in the two other groups. However, there was no change in the expression of adhesion molecules CD29 and CD11a on lymphocytes in either of the groups. This study provides further evidence that HS can modify lymphocyte and eosinophil functions.

Eighteen children with perennial asthma and allergy to house-dust mite (HDM) underwent a bronchial challenge with HDM. Before and 24 h after the test, a venous blood sample was taken to determine levels of eosinophils, eosinophil cationic protein (ECP), soluble interleukin-2 receptor (IL-2R), and interleukin-6 (IL-6). A histamine challenge was performed before and 24 h after the HDM challenge. All subjects showed an immediate asthmatic reaction (IAR). A definite late asthmatic reaction (LAR) was observed in 15 children, a probable LAR in two, and no LAR in one. Because of persistent bronchial obstruction (FEV1 < 70%), eight children were unable to perform a histamine challenge 24 h after the allergen challenge. These were the children with the lowest prechallenge provocation dose (PD20) of histamine. In the other 10 children, the mean PD20 histamine decreased after the HDM challenge (mean PD20 before was 0.56 mg/ml; after challenge it was 0.14 mg/ml; P = 0.007). After the HDM challenge, an increase was detected in the mean values of blood eosinophils (mean before was 446/mm3; mean after was 733/mm3; P = 0.002), ECP (mean before was 26.3 micrograms/l; mean after was 34.3 micrograms/l; P < 0.040), and IL-2R (mean before was 116.35 U/ml; mean after was 128.52 U/ml; P < 0.040). On the other hand, IL-6 remained unchanged after the HDM challenge (mean before was 9.47 pg/l; mean after was 9.70 pg/l; P = 0.360).(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-three patients with type I allergic respiratory diseases received aqueous grass pollen immunotherapy in a prospective study designed to compare the clinical and biological effects of a semi-rush hyposensitization (20 patients) with ordinary hyposensitization (23 patients). Before the start of the therapy (end of previous grass pollen season, t1) and before (t2) and after the next grass pollen season (t3), total serum IgE (tIgE), grass pollen-specific IgE (GPsIgE), grass pollen-specific IgG (GPsIgG) and complement factors C3 and C4 were determined. GPsIgE and GPsIgG levels increased significantly more during immunotherapy in patients receiving the semi-rush scheme as compared with the ordinary scheme. There were no significant changes between the two schemes at any times for tIgE, C3 and C4. GPsIgG was already higher in allergic patients before the start of therapy as compared with non-allergic patients and controls. Clinical improvement was the same in patients treated with the semi-rush scheme as in the ordinary group. The number of side effects was not statistically different between the two groups. In neither group was there a correlation between the change in biological parameters and change in clinical symptoms. As the semi-rush scheme gives the same results immunologically as well as clinically, it could be used in a number of patients since it reduces the time course of the initial therapy by about 2 months.