BACKGROUNDCannabis allergy (CA) has mainly been attributed to Can s 3, the nsLTP (non-specific lipid transfer proten) of Cannabis sativa. Nevertheless, standardized diagnostic tests are lacking and research on CA is scarce. OBJECTIVETo explore the performance of five cannabis diagnostic tests and the phenotypic profile of CA. METHODS120 CA patients were included and stratified according to the nature of their cannabis-related symptoms, 62 healthy and 189 atopic controls were included. Specific (s)IgE hemp, sIgE and BAT rCan s 3, BAT with a crude cannabis extract and a skin prick test (SPT) with a nCan s 3-rich cannabis extract were performed. Clinical information was based on patient-history and a standardized questionnaire. RESULTSFirstly, up to 72% of CA reporting likely-anaphylaxis (CA-A) are Can s 3 sensitized. Actually, the Can s 3-based diagnostic tests show the best combination of positive and negative predictive values; 80% and 60%, respectively. sIgE hemp displays 82% sensitivity but only 32% specificity. Secondly, Can s 3+CA reported significantly more cofactor mediated reactions and displayed significantly more sensitizations to other nsLTPs than Can s 3-CA. Finally, the highest prevalence of systemic reactions to plant-derived foods was seen in CA-A, namely 72%.

In conclusion, IL-33, and in a lesser extent IL-6, prime individual MCs for subsequent IgE-mediated activation. Moreover, this priming effect is synergistic. In contrast, none of the cytokines had a priming effect on MRGPRX2-mediated activation of MCs. © 2017 International Clinical Cytometry Society.

Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs.

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.

Peripheral blood cultured mast cells (PBCMCs) are defined as CD117 +ve CD203c +ve cells. PBCMCs harbour two subpopulations: cells with surface expression ofMRGPRX2 (MRGPRX2 +ve) and cells without expression ofMRGPRX2 (MRGPRX2-ve).

No abstract

BAT: basophil activation test FcεRI: high affinity receptor for sIgE IDT: intradermal test MC: mast cell MCA + : mast cell activation MCA -: no mast cell activation ROC ST+ : positive skin test rocuronium ROC ST-: negative skin test rocuronium ROC BAT+ : positive BAT rocuronium ROC BAT-: negative BAT rocuronium ROC BATNR : non-responder in BAT rocuronium NMBA: neuromuscular blocking agent NPV: negative predictive value POH: perioperative hypersensitivity PPV: positive predictive value sIgE: specific IgE antibody SPT: skin prick test ORCID

No abstract