21 results on '"Torres MJ"'
Search Results
2. Changing patterns in the epidemiology of drug allergy.
- Author
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Doña I, Torres MJ, Celik G, Phillips E, Tanno LK, and Castells M
- Subjects
- Adult, Child, Humans, Quality of Life, Penicillins adverse effects, Anti-Bacterial Agents, Drug Hypersensitivity diagnosis, Drug Hypersensitivity epidemiology, Anaphylaxis diagnosis
- Abstract
Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. Underdiagnosis and overdiagnosis are common and due to the lack of standardized definitions and biomarkers. The true burden of DA is unknown, and recent efforts in data gathering through electronic medical records are starting to provide emerging patterns around the world. Ten percent of the general population engaged in health care claim to have a DA, and the most common label is penicillin allergy. Up to 20% of emergency room visits for anaphylaxis are due to DA and 15%-20% of hospitalized patients report DA. It is estimated that DA will increase based on the availability and use of new and targeted antibiotics, vaccines, chemotherapies, biologicals, and small molecules, which are aimed at improving patient's options and quality of life. Global and regional variations in the prevalence of diseases such as human immunodeficiency virus and mycobacterial diseases, and the drugs used to treat these infections have an impact on DA. The aim of this review is to provide an update on the global impact of DA by presenting emerging data on drug epidemiology in adult and pediatric populations., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2024
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3. Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study.
- Author
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Céspedes JA, Fernández-Santamaría R, Ariza A, Bogas G, Doña I, Rondón C, Salas M, Labella M, Frecha C, Mayorga C, Torres MJ, and Fernández TD
- Subjects
- Humans, Amoxicillin adverse effects, Prospective Studies, Basophils, Basophil Degranulation Test methods, Clavulanic Acid, Tetraspanin 30, Hypersensitivity, Immediate diagnosis, Anaphylaxis diagnosis, Anaphylaxis etiology
- Abstract
Background: Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE-mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high-risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta-lactams, although controversy exists regarding the best activation marker. We have performed a real-life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs., Methods: We prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX-CLV administration during a 6-year period. The allergological work-up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers., Results: In AX-allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like-hood ratio. In CLV-allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c., Conclusions: BAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work-up in 46.6% of patients, diminishing the risk of reinducing allergic reactions., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2023
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4. Risk stratification through extensive allergy work-up in COVID-19-mRNA vaccine allergic reactions.
- Author
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Soria A, Labella M, Doña I, Nicaise-Roland P, Chollet-Martin S, Autegarden JE, Castagna J, Le Thai C, de Chaisemartin L, Torres MJ, and Barbaud A
- Subjects
- Humans, Risk Assessment, mRNA Vaccines, COVID-19 prevention & control, Hypersensitivity diagnosis, Hypersensitivity etiology, Anaphylaxis
- Published
- 2023
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5. A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice.
- Author
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Núñez R, Rodríguez MJ, Lebrón-Martín C, Martín-Astorga MDC, Ramos-Soriano J, Rojo J, Torres MJ, Cañas JA, and Mayorga C
- Subjects
- Animals, Mice, T-Lymphocytes, Regulatory, Allergens metabolism, DNA Methylation, Forkhead Transcription Factors metabolism, Food Hypersensitivity therapy, Anaphylaxis metabolism
- Abstract
Introduction: Lipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated., Methods: It was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice., Results: Most of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4 , Stat5a , Stat5b , Foxp3 , and Gata3 . In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice., Discussion: In conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Núñez, Rodríguez, Lebrón-Martín, Martín-Astorga, Ramos-Soriano, Rojo, Torres, Cañas and Mayorga.)
- Published
- 2023
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6. Resensitization in suspected penicillin allergy.
- Author
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Doña I, Guidolin L, Bogas G, Olivieri E, Labella M, Schiappoli M, Sáenz de Santa María R, Dama A, Salas M, Senna G, Bonadonna P, and Torres MJ
- Subjects
- Humans, Skin Tests methods, Immunoglobulin E, Penicillins adverse effects, Sodium Tetradecyl Sulfate, Anti-Bacterial Agents adverse effects, Anaphylaxis diagnosis, Anaphylaxis chemically induced, Drug Hypersensitivity diagnosis
- Abstract
Background: The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies., Objectives: To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE)., Material and Methods: Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks., Results: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009)., Conclusions: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2023
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7. Drug-induced Anaphylaxis.
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Labella M, de Santa María RS, Bogas G, Salas M, Fernández TD, Mayorga C, Torres MJ, and Doña I
- Subjects
- Humans, Biomarkers, Allergens, Skin Tests, Anaphylaxis chemically induced, Anaphylaxis diagnosis, Anaphylaxis drug therapy, Drug Hypersensitivity diagnosis, Drug Hypersensitivity therapy, Hypersensitivity, Immediate diagnosis
- Abstract
Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place in the setting of illness and/or polypharmacotherapy. To review the most recent findings in the diagnosis and management of immediate drug hypersensitivity reactions. Studies were selected based on their relevance, originality and date of publication. The understanding of endotypes, biomarkers and phenotypes has improved the categorization of immediate hypersensitivity reactions. In this review, we discussed the short- and long-term management of anaphylaxis with a special focus on in vivo and in vitro diagnostic methods. Moreover, the clinical management of drug-induced anaphylaxis, the role of hidden allergens and the importance of delabeling are discussed. Endophenotyping is crucial to correctly diagnose and treat patients with immediate drug hypersensitivity reactions, preventing future episodes through drug desensitization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
- Full Text
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8. Methylation changes induced by a glycodendropeptide immunotherapy and associated to tolerance in mice.
- Author
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Núñez R, Rodríguez MJ, Lebrón-Martín C, Martín-Astorga MDC, Palomares F, Ramos-Soriano J, Rojo J, Torres MJ, Cañas JA, and Mayorga C
- Subjects
- Animals, Mice, Methylation, Allergens, Desensitization, Immunologic, Food Hypersensitivity, Sublingual Immunotherapy, Anaphylaxis
- Abstract
Introduction: Allergen-specific immunotherapy (AIT) is applied as treatment to rise tolerance in patients with food allergies. Although AIT is thoroughly used, the underlying epigenetic events related to tolerant induction are still unknown. Thus, we aim to investigate epigenetic changes that could be related to tolerance in dendritic cells (DCs) from anaphylactic mice to lipid transfer proteins, Pru p 3, in the context of a sublingual immunotherapy (SLIT) with a glycodendropeptide (D1ManPrup3) that has demonstrated tolerant or desensitization responses depending on the treatment dose., Methods: Changes in DNA methylation in CpG context were determined comparing Sensitized (Antigen-only) animals and two groups receiving SLIT with the D1ManPrup3 nanostructure (D1ManPrup3-SLIT): Tolerant (2nM D1ManPrup3) and Desensitized (5nM D1ManPrup3), against anaphylactic animals. DNA from lymph nodes-DCs were isolated and then, Whole Genome Bisulphite Sequencing was performed to analyze methylation., Results: Most differentially methylated regions were found on the area of influence of gene promoters (DMPRs). Compared to the Anaphylactic group, the highest value was found in Desensitized mice (n = 7,713 DMPRs), followed by Tolerant (n = 4,091 DMPRs) and Sensitized (n = 3,931 DMPRs) mice. Moreover, many of these epigenetic changes were found in genes involved in immune and tolerance responses (Il1b, Il12b, Il1a, Ifng, and Tnf) as shown by functional enrichment (DCs regulation, B cell-mediated immunity, and effector mechanisms)., Discussion: In conclusion, different doses of D1ManPrup3-SLIT induce different DNA methylation changes, which are reflected in the induction of distinct responses, tolerance, or desensitization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Núñez, Rodríguez, Lebrón-Martín, Martín-Astorga, Palomares, Ramos-Soriano, Rojo, Torres, Cañas and Mayorga.)
- Published
- 2022
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9. Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.
- Author
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Barbaud A, Garvey LH, Arcolaci A, Brockow K, Mori F, Mayorga C, Bonadonna P, Atanaskovic-Markovic M, Moral L, Zanoni G, Pagani M, Soria A, Jošt M, Caubet JC, Carmo A, Mona AA, Alvarez-Perea A, Bavbek S, Benedetta B, Bilo MB, Blanca-López N, Bogas HG, Buonomo A, Calogiuri G, Carli G, Cernadas J, Cortellini G, Celik G, Demir S, Doña I, Dursun AB, Eberlein B, Faria E, Fernandes B, Garcez T, Garcia-Nunez I, Gawlik R, Gelincik A, Gomes E, Gooi JHC, Grosber M, Gülen T, Hacard F, Hoarau C, Janson C, Johnston SL, Joerg L, Kepil Özdemir S, Klimek L, Košnik M, Kowalski ML, Kuyucu S, Kvedariene V, Laguna JJ, Lombardo C, Marinho S, Merk H, Meucci E, Morisset M, Munoz-Cano R, Murzilli F, Nakonechna A, Popescu FD, Porebski G, Radice A, Regateiro FS, Röckmann H, Romano A, Sargur R, Sastre J, Scherer Hofmeier K, Sedláčková L, Sobotkova M, Terreehorst I, Treudler R, Walusiak-Skorupa J, Wedi B, Wöhrl S, Zidarn M, Zuberbier T, Agache I, and Torres MJ
- Subjects
- Humans, Vaccines, Synthetic, mRNA Vaccines, Anaphylaxis diagnosis, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Drug Hypersensitivity diagnosis, Drug Hypersensitivity etiology, Drug Hypersensitivity therapy, Vaccines
- Abstract
Background: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized., Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed., Results: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable., Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)
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- 2022
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10. Anaphylaxis and Pregnancy: A Systematic Review and Call for Public Health Actions.
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Carra S, Schatz M, Mertes PM, Torres MJ, Fuchs F, Senna G, Castells MC, Demoly P, and Tanno LK
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- Cesarean Section, Female, Humans, Infant, Newborn, Pregnancy, Public Health, Anaphylaxis epidemiology, Pregnancy Complications epidemiology
- Abstract
Background: Although rare, anaphylaxis during pregnancy implies a risk to both mothers and newborns., Objective: This systematic review is intended to identify key issues in the diagnosis and management of this condition to support prevention strategies and decrease the risk for death related to anaphylaxis during pregnancy., Methods: We searched MEDLINE, Cochrane, LILACS, SciELO, and Science Direct databases for manuscripts concerning the term "anaphylaxis during pregnancy," without language restrictions. We screened studies, extracted data, and assessed the risk for bias independently in duplicate., Results: We selected 12 articles. Frequency of anaphylaxis during maternity was estimated to be 1.5 to 3.8 per 100,000 pregnancies. Only one study provided anaphylaxis mortality data in pregnant women; the rate of anaphylaxis-related maternal mortality was estimated at 0.05/100,000 live births. No standard definition of anaphylaxis severity has been used. A total of 49% to 74% of anaphylaxis cases were described during caesarean section. Beta-lactam antibiotics (58%), latex (25%), and anesthetic agents (17%) were the main causes. In 17% of reports, causative agents were proven by allergy testing. Moreover, 72% of articles proposed the same management and treatment for a clinical episode of anaphylaxis during pregnancy as for nonpregnant patients, and the use of epinephrine in the patient's care during anaphylaxis in pregnancy., Conclusions: Few studies address anaphylaxis during pregnancy. Most have been produced by nonallergy specialists. Collaboration among different specialists involved in the care of pregnant women should be established to support preventive strategies and reduce avoidable deaths., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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11. Polymorphisms in CEP68 gene associated with risk of immediate selective reactions to non-steroidal anti-inflammatory drugs.
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Perkins JR, Acosta-Herrera M, Plaza-Serón MC, Jurado-Escobar R, Doña I, García-Martín E, Isidoro-García M, Bartra J, Ribas-Perez D, Mayorga C, Torres MJ, Flores C, and Cornejo-García JA
- Subjects
- Adult, Anaphylaxis chemically induced, Anaphylaxis pathology, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Drug Hypersensitivity pathology, Female, Genetic Association Studies, Humans, Inflammation drug therapy, Inflammation genetics, Inflammation pathology, Male, Polymorphism, Single Nucleotide genetics, Risk Factors, Urticaria chemically induced, Urticaria pathology, Anaphylaxis genetics, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Drug Hypersensitivity genetics, Microtubule-Associated Proteins genetics, Urticaria genetics
- Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions. Such reactions can be pharmacologically or immunologically mediated, but in both cases individual susceptibility can be influenced by genetic factors. Polymorphisms in centrosomal protein of 68 kDa (CEP68) have been associated with pharmacologically mediated NSAIDs reactions. Here, we evaluated this gene in immunologically mediated single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) by analyzing 52 single nucleotide polymorphisms in CEP68 in 176 patients and 363 NSAIDs-tolerant controls. Two intronic variants (rs2241160 and rs2241161) were significantly associated with an increased risk of SNIUAA, suggesting CEP68 to be a key player in both types of NSAIDs hypersensitivity. However, we found no overlap with genetic variants previously associated with pharmacologically mediated hypersensitivity, pointing to a complex role for this gene and its potential use in the development of biomarkers of clinical utility to diagnose patients at risk of these reactions and to differentiate entities.
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- 2019
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12. Glycosylated nanostructures in sublingual immunotherapy induce long-lasting tolerance in LTP allergy mouse model.
- Author
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Rodriguez MJ, Ramos-Soriano J, Perkins JR, Mascaraque A, Torres MJ, Gomez F, Diaz-Perales A, Rojo J, and Mayorga C
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- Anaphylaxis immunology, Animals, Antigens, Plant adverse effects, Antigens, Plant immunology, Dendritic Cells drug effects, Dendritic Cells immunology, Disease Models, Animal, Food Hypersensitivity immunology, Glycosylation drug effects, Humans, Mice, Nanostructures administration & dosage, Nanostructures chemistry, Prunus persica immunology, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory immunology, Anaphylaxis drug therapy, Food Hypersensitivity drug therapy, Prunus persica adverse effects, Sublingual Immunotherapy methods
- Abstract
An effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs). We propose a novel sublingual immunotherapy for peach allergy, using systems, that combine Prup3-T-cell peptides with mannose dendrons (D
1 ManPrup3 and D4 ManPrup3). Peach anaphylactic mice were treated 1, 2 and 5 nM concentrations. Tolerance was assessed one/five weeks after finishing treatment by determining in vivo/in vitro parameters after challenge with Prup3. Only mice receiving D1 ManPrup3 at 2 nM were protected from anaphylaxis (no temperature changes, decrease in Prup3-sIgE and -sIgG1 antibody levels, and secreting cells) compared to PBS-treated mice. Moreover, an increase of Treg-cells and regulatory cytokines (IL-10+ /IFN-γ+ ) in CD4+ -T-cells and DCs were found. These changes were maintained at least five weeks after stopping treatment. D1 ManPrup3 is an effective new approach of immunotherapy inducing protection from anaphylaxis which persists after finishing treatment.- Published
- 2019
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13. Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food-Antigen-Induced Anaphylaxis Reveals the Upregulation of Multiple Immune-Related Pathways.
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Rodriguez MJ, Palomares F, Bogas G, Torres MJ, Diaz-Perales A, Rojo J, Plaza-Seron MDC, Rodriguez-Nogales A, Orengo C, Mayorga C, and Perkins JR
- Subjects
- Animals, Dendritic Cells immunology, Female, Gene Expression Profiling, Gene Ontology, Humans, Immunoglobulin E blood, Interleukin-10 physiology, Mice, Mice, Inbred BALB C, Sequence Analysis, RNA, Up-Regulation, Anaphylaxis etiology, Antigens, Plant immunology, Dendritic Cells metabolism, Food Hypersensitivity etiology, Plant Proteins immunology
- Abstract
Scope: Much of the knowledge about gene expression during anaphylaxis comes from candidate gene studies. Despite their potential role, expression changes in dendritic cells (DCs) have not been studied in this context using high throughput methods. The molecular mechanisms underlying food-antigen-induced anaphylaxis are investigated using DCs from an animal model., Methods and Results: RNA sequencing is used to study gene expression in lymph-node-derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3 during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least twofold changes. Almost three-quarters of these increase during anaphylaxis. A subset is confirmed using RT-PCR in a second set of samples obtained from a new batch of mice. Enrichment analysis shows an overrepresentation of genes involved in key immune system and inflammatory processes, including TGF-β signaling. Comparison with a study using anaphylactic human subjects show significant overlap., Conclusions: The findings provide a comprehensive overview of the transcriptional changes occurring in DCs during anaphylaxis and help elucidate the mechanisms involved. They add further weight to the putative role of these cells in anaphylaxis and highlight genes that may represent potential therapeutic targets., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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14. The urgent need for a harmonized severity scoring system for acute allergic reactions.
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Muraro A, Fernandez-Rivas M, Beyer K, Cardona V, Clark A, Eller E, Hourihane JOB, Jutel M, Sheikh A, Agache I, Allen KJ, Angier E, Ballmer-Weber B, Bilò MB, Bindslev-Jensen C, Camargo CA Jr, Cianferoni A, DunnGalvin A, Eigenmann PA, Halken S, Hoffmann-Sommergruber K, Lau S, Nilsson C, Poulsen LK, Rueff F, Spergel J, Sturm G, Timmermans F, Torres MJ, Turner P, van Ree R, Wickman M, Worm M, Mills ENC, and Roberts G
- Subjects
- Allergens immunology, Anaphylaxis immunology, Disease Management, Health Services Needs and Demand, Humans, Hypersensitivity immunology, Immunoglobulin E immunology, Practice Guidelines as Topic, Severity of Illness Index, Anaphylaxis diagnosis, Hypersensitivity diagnosis
- Abstract
The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)
- Published
- 2018
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15. Practical Guidelines for Perioperative Hypersensitivity Reactions.
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Laguna JJ, Archilla J, Doña I, Corominas M, Gastaminza G, Mayorga C, Berjes-Gimeno P, Tornero P, Martin S, Planas A, Moreno E, and Torres MJ
- Subjects
- Anaphylaxis etiology, Anesthetics therapeutic use, Consensus, Drug Hypersensitivity drug therapy, Humans, Intraoperative Complications drug therapy, Practice Guidelines as Topic, Societies, Medical, Spain, Allergy and Immunology, Anaphylaxis prevention & control, Anesthesia adverse effects, Anesthetics adverse effects, Drug Hypersensitivity diagnosis, Intraoperative Complications diagnosis
- Abstract
Perioperative hypersensitivity reactions constitute a first-line problem for anesthesiologists and allergists. Therefore, hospitals should have a consensus protocol for the diagnosis and management of these reactions. However, this kind of protocol is not present in many hospitals, leading to problems with treatment, reporting of incidents, and subsequent etiological diagnosis. In this document, we present a systematic review of the available scientific evidence and provide general guidelines for the management of acute episodes and for referral of patients with perioperative hypersensitivity reactions to allergy units. Members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) have created this document in collaboration with members of the Spanish Anesthesia Society (SEDAR). A practical algorithm is proposed for the etiologic diagnosis, and recommendations are provided for the management of hypersensitive patients.
- Published
- 2018
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16. LPS promotes Th2 dependent sensitisation leading to anaphylaxis in a Pru p 3 mouse model.
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Rodriguez MJ, Aranda A, Fernandez TD, Cubells-Baeza N, Torres MJ, Gomez F, Palomares F, Perkins JR, Rojo J, Diaz-Perales A, and Mayorga C
- Subjects
- Anaphylaxis pathology, Animals, Antibodies immunology, Antibody Specificity immunology, Antigens, Plant immunology, Cell Proliferation, Disease Models, Animal, Enzyme-Linked Immunospot Assay, Female, Immunoglobulin E immunology, Immunoglobulin G immunology, Lipopolysaccharides, Mice, Inbred BALB C, Spleen pathology, Anaphylaxis immunology, Immunization
- Abstract
Pru p 3 is the major peach allergen in the Mediterranean area. It frequently elicits severe reactions, limiting its study in humans, raising the need for animal models to investigate the immunological mechanisms involved. However, no anaphylaxis model exists for Pru p 3. We aimed to develop a model of peach anaphylaxis by sensitising mice with Pru p 3 in combination with lipopolysaccharide (LPS) as an adjuvant. Four groups of mice were sensitised intranasally: untreated; treated with Pru p 3; treated with LPS; treated with Pru p 3 + LPS. After sensitisation mice were intraperitoneally challenged with Pru p 3 and in vivo and in vitro parameters were evaluated. Only mice in the Pru p 3 + LPS group showed anaphylaxis symptoms, including a decrease in temperature. Determination of in vitro parameters showed a Th2 response with an increase of Pru p 3-specific IgE and IgG1. Moreover, at the cellular level, we found increased levels of IgE and IgG1 secreting Pru p 3-specific cells and a proliferative CD4
+ T-cell response. These results demonstrate that Pru p 3-specific anaphylaxis can be generated after nasal sensitisation to Pru p 3 in combination with LPS. This is a promising model for evaluating food allergy immunotherapies., Competing Interests: The authors declare no competing financial interests.- Published
- 2017
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17. Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified.
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Pérez-Alzate D, Cornejo-García JA, Pérez-Sánchez N, Andreu I, García-Moral A, Agúndez JA, Bartra J, Doña I, Torres MJ, Blanca M, Blanca-López N, and Canto G
- Subjects
- Adolescent, Adult, Aged, Anaphylaxis chemically induced, Anaphylaxis immunology, Angioedema chemically induced, Angioedema immunology, Anti-Inflammatory Agents, Non-Steroidal immunology, Aspirin immunology, Cross Reactions, Drug Hypersensitivity immunology, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Reproducibility of Results, Spain, Urticaria chemically induced, Urticaria immunology, Young Adult, Anaphylaxis diagnosis, Angioedema diagnosis, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Aspirin administration & dosage, Drug Hypersensitivity diagnosis, Immune Tolerance, Immunologic Tests, Urticaria diagnosis
- Abstract
Background and Objectives: Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors., Methods: Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration., Results: From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients., Conclusions: Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.
- Published
- 2017
- Full Text
- View/download PDF
18. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole.
- Author
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Ariza A, García-Martín E, Salas M, Montañez MI, Mayorga C, Blanca-Lopez N, Andreu I, Perkins J, Blanca M, Agúndez JA, and Torres MJ
- Subjects
- Adult, Aged, Aminopyrine analogs & derivatives, Aminopyrine metabolism, Aminopyrine pharmacology, Ampyrone analogs & derivatives, Ampyrone metabolism, Ampyrone pharmacology, Anaphylaxis immunology, Anaphylaxis physiopathology, Anti-Inflammatory Agents, Non-Steroidal metabolism, Basophil Degranulation Test, Basophils immunology, Biotransformation, Case-Control Studies, Dipyrone metabolism, Female, Humans, Male, Middle Aged, Pilot Projects, Primary Cell Culture, Anaphylaxis chemically induced, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Basophils drug effects, Dipyrone adverse effects
- Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.
- Published
- 2016
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19. Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid.
- Author
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Pineda F, Ariza A, Mayorga C, Arribas F, González-Mendiola R, Blanca-López N, Davila G, Cabañes N, Canto G, Laguna JJ, Senent C, Stahl-Skov P, Palacios R, Blanca M, and Torres MJ
- Subjects
- Adolescent, Adult, Aged, Anaphylaxis chemically induced, Anaphylaxis immunology, Anaphylaxis pathology, Angioedema chemically induced, Angioedema immunology, Angioedema pathology, Biological Assay, Case-Control Studies, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Skin Tests, Time Factors, Anaphylaxis diagnosis, Angioedema diagnosis, Anti-Bacterial Agents adverse effects, Clavulanic Acid adverse effects, Histamine Release, Monitoring, Immunologic methods
- Abstract
Background: Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help evaluate patients with selective hypersensitivity to CLV., Methods: Eighteen patients with immediate selective hypersensitivity reactions to CLV (positive skin tests to CLV but negative to the major and minor determinants of benzylpenicillin and amoxicillin; negative DPT to benzylpenicillin and amoxicillin) and 21 controls with tolerance to CLV were included. Direct and passive HRT, using patient whole blood or 'IgE-stripped' donor blood sensitized by patient serum, respectively, were performed by stimulating the blood with CLV, and basophil histamine release was detected by fluorometric determination., Results: The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We obtained similar data for both the direct and passive HRT, with a sensitivity and specificity of 55 and 85%, respectively, a positive predictive value of 76% and a negative predictive value of 69%., Conclusions: The sensitivity of both the direct and passive HRT for diagnosing patients with immediate allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples., (© 2016 S. Karger AG, Basel.)
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- 2015
- Full Text
- View/download PDF
20. Update on Quinolone Allergy
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Doña I, Moreno, E, Perez-Sanchez, N, ANDREU, INMACULADA, HERNANDEZ, MARÍA DOLORES, and Torres, MJ
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Quinolone ,Skin test ,Basophil activation test ,Maculopapular exanthema ,Drug provocation test ,Anaphylaxis - Abstract
Purpose of Review Quinolones are a group of synthetic antibiotics widely use as first-line treatment for many infections. There has been an increase in the incidence of hypersensitivity reactions to quinolones in recent years, likely due to increased prescription. The purpose of this review is to summarize the clinical pictures, the methods used for diagnosing and the management of allergic reactions to quinolones. Recent Findings Allergic reactions to quinolones can be immediate or delayed, being anaphylaxis and maculopapular exanthema respectively the most frequent clinical entities. A precise diagnosis is particularly difficult since clinical history is often unreliable, skin tests can induce false-positive results, and commercial in vitro test are not well validated. Therefore, drug provocation testing is considered the gold standard to establish diagnosis, which is not a risk-free procedure. Cross-reactivity between quinolones is difficult to predict due to the small number of patients included in the few published studies. Moreover, hypersensitivity to quinolones has also been associated with beta-lactam and neuromuscular blocking agent allergies, although further studies are needed to understand the underlying mechanisms. Avoidance of the culprit quinolone is indicated in patients with a diagnosis of hypersensitivity to these drugs. When quinolone treatment is the only therapeutic option available, desensitization is necessary. Summary This review summarizes the complex diagnostic approach and management of allergic reactions to quinolones.
- Published
- 2017
21. Evaluation of Subjects Experiencing Allergic Reactions to Non-Steroidal Anti-Inflammatory Drugs: Clinical Characteristics and Drugs Involved
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Natalia Pérez-Sánchez, Inmaculada Doña, Gador Bogas, María Salas, Almudena Testera, José A. Cornejo-García, María J. Torres, [Pérez-Sánchez,N, Doña,I, Bogas,G, Salas,M, Testera,A, Torres, MJ] Allergy Unit, Malaga Regional University Hospital, Malaga, Spain. [Pérez-Sánchez,N, Torres, MJ] Departamento de Medicina, Universidad de Málaga, Malaga, Spain. [Cornejo-García,JA, Torres, MJ] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, ARADyAL, Malaga, Spain. [Torres, MJ] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Malaga, Spain., This work was supported by grants co-funded by the European Regional Development Fund (ERDF), from the Carlos III National Health Institute (ARADyAL network RD16/0006/0001, and PI17/01593), and from the Sociedad Española de Alergoloǵıa e Inmunoloǵıa Cĺınica (SEAIC, and Ref. Convocatoria Ayudas 2016, and Convocatoria Ayudas 2018 REF: 18B02).
- Subjects
0301 basic medicine ,Urticaria ,Provocation test ,Clinical immunology ,Anafilaxia ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoles::Pyrazolones [Medical Subject Headings] ,Medicine ,non-steroidal anti-inflammatory drugs ,Pharmacology (medical) ,media_common ,Original Research ,Chemicals and Drugs::Pharmaceutical Preparations [Medical Subject Headings] ,Drug eruption ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,030220 oncology & carcinogenesis ,Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity::Drug Eruptions [Medical Subject Headings] ,medicine.symptom ,Hipersensibilidad a las drogas ,Anaphylaxis ,Non-steroidal anti-inflammatory drugs ,Drug ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Exanthema [Medical Subject Headings] ,medicine.medical_specialty ,media_common.quotation_subject ,Drug allergy ,Diseases::Immune System Diseases::Hypersensitivity [Medical Subject Headings] ,Culprit ,03 medical and health sciences ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Urticaria [Medical Subject Headings] ,anaphylaxis ,Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Pharmacology ,Angioedema ,urticarial ,business.industry ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal [Medical Subject Headings] ,lcsh:RM1-950 ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Anaphylaxis [Medical Subject Headings] ,medicine.disease ,Dermatology ,Urticarial ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Non steroidal anti inflammatory ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Urticaria::Angioedema [Medical Subject Headings] ,business ,Antiinflamatorios no esteroideos ,drug allergy ,clinical immunology - Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs), the most commonly prescribed and consumed medicines worldwide, are the main triggers of drug hypersensitivity reactions (DHRs). The underlying mechanisms of NSAID-DHRs may be related to COX-1 inhibition (cross-hypersensitivity reactions, CRs) or to immunological recognition (selective reactions, SRs), being the latter remarkably less studied. SRs include those usually appearing within the first hour after drug intake (single-NSAID-induced urticaria/angioedema or anaphylaxis, SNIUAA), and those usually occurring more than 24 h after (single-NSAID-induced delayed reactions, SNIDR). We have evaluated the largest series of patients with SRs, analyzing the number of episodes and drugs involved, the latency for reaction onset, the clinical entities, among other variables, as well as the value of available diagnostic methods. Globally, pyrazolones and arylpropionics were the most frequent culprits (39.3% and 37.3%, respectively). Pyrazolones were the most frequent triggers in SNIUAA and arylpropionics in SNIDR. Urticaria was the most common clinical entity in SNIUAA (42.4%) followed by anaphylaxis (33.3%); whereas SNIDR induced mostly fixed drug eruption (41.1%) and maculopapular exanthema (32.6%). The percentage of patients diagnosed by clinical history was higher in SNIUAA compared with SNIDR (62.7% versus 35.3%, p = 0.00015), whereas the percentage of those diagnosed by skin tests was higher in SNIDR than in SNIUAA (47.1% versus 22.8%, p = 0.00015). Drug provocation test with the culprit was performed in 67 SNIUAA (14.5%) and in 9 SNIDR (17.6%) patients. Our results may be of interest not only for allergologists but also for other clinicians dealing with these drugs, and can be useful for the correct identification of subjects experiencing DHRs to NSAIDs, and for avoiding mislabeling. Moreover, as NSAIDs are highly consumed worldwide, our results may be of interest for evaluating other populations exposed to these drugs. Yes
- Published
- 2020
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