9 research outputs found

    Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins

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    Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillinsThis research was funded by the Institute of Health ‘Carlos III’ (ISCIII) of the Ministry of Economy and Competitiveness (MINECO) (grants cofunded by European Regional Development Fund: PI15/01206, PI17/01237, PI18/00095, RETICS ARADYAL RD16/0006/0001). Andalusian Regional Ministry of Health (grants PE-0172-2018, PI-0127-2020). DrNanoDall project by ISCIII thorough AES 2019 within the ERANET-EuroNanoMed-III framework (AC19/00082). AA holds a Senior Postdoctoral Contract (RH-0099-2020) with the Andalusian Regional Ministry of Health (cofunded by European Social Fund (ESF): “Andalucía se mueve con Europa”). ML holds a “Rio Hortega” contract (CM20/00210), GB and N.P.-S. hold a “Juan Rodés” (JR18/00054 and JR21/00024, respectively) with ISCIII of MINECO (cofunded by ESF). CM holds a ‘Nicolas Monardes’ research contract with the Andalusian Regional Ministry Health (RC-0004-2021). Partial funding for open access charge: Universidad de Málag

    In Vitro Diagnostic Testing for Antibiotic Allergy.

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    Allergy to antibiotics is an important worldwide problem, with an estimated prevalence of up to 10% of the population. Reaction patterns for different antibiotics have changed in accordance with consumption trends. Most of the allergic reactions to antibiotics have been reported for betalactams, followed by quinolones and macrolides and, to a lesser extent, to others, such as metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a detailed clinical history, which is not always possible and can be unreliable. This is usually followed by in vivo, skin, and drug provocation tests. These are not recommended for severe, potentially lifethreaten reactions or for drugs that are known to produce a high rate of false positive results. Given the limitations of in vivo tests, in vitro test can be helpful for diagnosis, despite having suboptimal sensitivity. The most highly employed techniques for diagnosing immediate reactions to antibiotics are immunoassays and basophil activation tests, while lymphocyte transformation tests are more commonly used to diagnose non-immediate reactions. In this review, we describe different in vitro techniques employed to diagnose antibiotic allergy

    Alternative Anaphylactic Routes: The Potential Role of Macrophages

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    Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators from effector cells. There are two potential pathways for anaphylaxis. The first one, IgE-dependent anaphylaxis, is induced by antigen (Ag) cross-linking of Ag-specific IgE bound to the high-affinity IgE receptor (FcεRI) on mast cells and basophils. The second one, IgG-dependent anaphylaxis is induced by Ag cross-linking of Ag-specific IgG bound to IgG receptors (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, and FcγRIIIA) on macrophages, neutrophils, and basophils. Macrophages exhibit a huge functional plasticity and are capable of exerting their scavenging, bactericidal, and regulatory functions under a wide variety of tissue conditions. Herein, we will review their potential role in the triggering and development of anaphylaxis. Thereby, macrophages, among other immune cells, play a role in both anaphylactic pathways (1) by responding to anaphylactic mediators secreted by mast cells after specific IgE cross-linking or (2) by acting as effector cells in the anaphylactic response mediated by IgG. In this review, we will go over the cellular and molecular mechanisms that take place in the above-mentioned anaphylactic pathways and will discuss the clinical implications in human allergic reactions.This work was supported by ISCIII (project numbers PI16/00249 and PI15/02256) cofounded by FEDER for the thematic network and cooperative research centers ARADyAL RD16/0006/0015 and RD16/0006/0001. This work was also supported by the Ministry of Economy and Competitiveness (project number SAF2014-52423-R) and by Fundación Mutua Madrileña (AP158912015). DR and was supported by FPI-CEU predoctoral fellowships.Peer reviewedPeer Reviewe

    Hypersensitivity to fluoroquinolones: The expression of basophil activation markers depends on the clinical entity and the culprit fluoroquinolone.

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    Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity-specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = -0.446; P

    Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response.

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    Journal Article; Research Support, Non-U.S. Gov't;Allergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to control its symptoms, however, up to 30% of patients may not respond. Previous studies of the immunological mechanisms involved in allergen-immunotherapy (AIT) have focused on the humoral and T-cell response and several studies have evaluated some B-cell subpopulations during AIT and their role in immunological tolerance. However, although B and plasma-cell subpopulations are two of the most important cellular subtypes involved in allergic reactions, their relation with AIT efficacy remains unelucidated. The objective was to analyze the effects of immunotherapy on different B and plasma-cell subpopulations and whether these changes correlate with the clinical response to the treatment. Although no changes are found in B-cell subpopulations, responder patients show increased levels of memory B-cells even before the beginning of treatment. Changes in plasma-cell subpopulations are found, mainly in circulating inflammatory plasma-cells that could affect the response to the allergen. Moreover, an early increase of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the determination of the memory B-cells before the initiation of the treatment, and the quantification of IgG4 and IgG4-secreting-cells in the first months of immunotherapy, could serve as markers for the clinical response to treatment.The study was funded by ISCIII-Thematic Networks and Co-operative Research Centers: RIRAAF (RD07/0064 and RD012/0013), Merck-Serono project, SEAIC Foundation, PI-0542-2010, Junta de Andalucía (CTS-7433) and Nicolas Monardes Program (C-0044-2012 SAS 2013), and ISCIII (PI12/02481) co-financed by the European Regional Development Fund -ERDFYe
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