430 results on '"Torres MJ"'
Search Results
2. Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset
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Freundt-Serpa, NP, primary, Salas-Cassinello, M, additional, Gonzalo-Fernández, A, additional, Marchán-Pinedo, N, additional, Doña, I, additional, Serrano-García, I, additional, Humanes-Navarro, AM, additional, Bogas, G, additional, Labella, M, additional, Sánchez-Morillas, L, additional, Torres, MJ, additional, and Fernández-Rivas, M, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization
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Vega, A, primary, Jimenez-Rodriguez, TW, additional, Barranco, R, additional, Bartra, J, additional, Diéguez, MC, additional, Doña, I, additional, Fernández-Rivas, M, additional, Gandolfo-Cano, M, additional, Gastaminza-Lasarte, G, additional, González-Mancebo, E, additional, de la Hoz Caballer, B, additional, Sánchez-Morillas, L, additional, Torres, MJ, additional, Berges-Gimeno, MP, additional, and Muñoz-Cano, R, additional
- Published
- 2021
- Full Text
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4. ARADyAL: The Spanish Multidisciplinary Research Network for Allergic Diseases
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Torres, MJ, primary, Agundez, J, additional, Barber, D, additional, Bartra, J, additional, Davila, I, additional, Escribese, MM, additional, Fernandez-Rivas, M, additional, Ferrer, M, additional, Perez-Inestrosa, E, additional, Villalba, M, additional, and Mayorga, C, additional
- Published
- 2021
- Full Text
- View/download PDF
5. Accuracy of the Diagnosis of Allergic Reactions in the Emergency Department
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Lacombe-Barrios, J, primary, Gómez, F, additional, Pérez, N, additional, Barrionuevo, E, additional, Doña, I, additional, Fernández Tahía, D, additional, Mayorga, C, additional, Torres, MJ, additional, Moreno, E, additional, Bogas, B, additional, and Salas, M, additional
- Published
- 2019
- Full Text
- View/download PDF
6. Practical Guidelines for Perioperative Hypersensitivity Reactions
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Laguna, JJ, primary, Archilla, J, additional, Doña, I, additional, Corominas, M, additional, Gastaminza, G, additional, Mayorga, C, additional, Berjes-Gimeno, P, additional, Tornero, P, additional, Martin, S, additional, Planas, A, additional, Moreno, E, additional, and Torres, MJ, additional
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- 2018
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7. The Role of Basophil Activation Test in Drug Allergy
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Fernandez-Santamaria R, G Bogas, M Salas, Laguna JJ, Fernandez TD, Torres MJ, and Mayorga C
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Medicine (miscellaneous) ,Immunology and Allergy - Published
- 2021
8. Basophil Histamine Release Induced by Amoxicilloyl-poly-L-lysine Compared With Amoxicillin in Patients With IgE-Mediated Allergic Reactions to Amoxicillin
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Arribas, F, primary, Falkencrone, S, additional, Sola, J, additional, Gomez-Serranillos, MP, additional, Laguna, JJ, additional, Montañez, MI, additional, Fernandez, TD, additional, Rodríguez, D, additional, Pineda, F, additional, Skov, PS, additional, Mayorga, C, additional, and Torres, MJ, additional
- Published
- 2017
- Full Text
- View/download PDF
9. Update on the Genetic Basis of Drug Hypersensitivity Reactions
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Jurado-Escobar, R, primary, Perkins, JR, additional, García-Martín, E, additional, Isidoro-García, M, additional, Doña, I, additional, Torres, MJ, additional, and Cornejo-García, JA, additional
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- 2017
- Full Text
- View/download PDF
10. 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, primary, Cornejo-García, JA, additional, Pérez-Sánchez, N, additional, Andreu, I, additional, García-Moral, A, additional, Agúndez, JA, additional, Bartra, J, additional, Doña, I, additional, Torres, MJ, additional, Blanca, M, additional, Blanca-López, N, additional, and Canto, G, additional
- Published
- 2017
- Full Text
- View/download PDF
11. Reglas de despacho en la programación de procedimientos quirúrgicos electivos: impacto en los indicadores de ocupación y oportunidad
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Estupiñán AM, Ana M., primary, Torres MJ, M. Juliana, additional, Caro MP, Martha P, additional, González-Neira EM, Eliana María, additional, Barrera D, David, additional, and Pérez N, Nicolás, additional
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- 2016
- Full Text
- View/download PDF
12. EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines
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Sokolowska M, Eiwegger T, Ollert M, Torres MJ, Barber D, Del Giacco S, Jutel M, Nadeau KC, Palomares O, Rabin RL, Riggioni C, Vieths S, Agache I, and Shamji MH
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SARS-CoV ,COVID ,virus - Abstract
The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.
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- 2021
13. Management of hypersensitivity reactions to chemotherapy and biologic agents: A survey of ARADyAL (Asthma, Adverse Drug Reactions and Allergy Network) Spanish allergy services
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Jimenez-Rodriguez TW, Berges-Gimeno MP, Barranco R, Bartra J, Diéguez MDC, Doña I, Fernández-Rivas M, Gandolfo-Cano MDM, Gastaminza-Lasarte G, González-Mancebo E, de la Hoz Caballer B, Sánchez-Morillas L, Torres MJ, Vega A, and Muñoz-Cano R
- Published
- 2021
14. Influence of in vitro capacitation time on structural and functional human sperm parameters
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Sàez-Espinosa P, Huerta-Retamal N, Robles-Gómez L, Avilés M, Aizpurua J, Velasco I, Romero A, and Gómez-Torres MJ
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endocrine system ,urogenital system ,reproductive and urinary physiology - Abstract
A cascade of dramatic physiological events is linked to the sperm acrosome reaction and binding to the oocyte's zona pellucida during human sperm capacitation. However, structural and functional sperm changes during capacitation currently remain poorly defined. Here, we performed a multibiomarker approach based on the utilization of sperm concentration, motility, viability, morphology, acrosome reaction, tyrosine phosphorylation, DNA fragmentation, and lectin-binding sites to analyze the impact caused by swim-up selection times (uncapacitated, 1 h capacitated, and 4 h capacitated) on sperm function and structure in normozoospermic samples. We found that a 4 h swim-up capacitation increased sperm quality, because a large number of cells with normal morphology and lower DNA fragmentation rates were recovered. Furthermore, the long-term capacitation induced a higher percentage of cells with tyrosine phosphorylation of the principal piece as well as a redistribution of lectin-binding sites. Overall, the multivariate biomarkers analyzed showed a less variable distribution on spermatozoa recovered after 4 h capacitation than that with the shorter capacitation time. These findings stress the importance of capacitation time as a relevant factor in sperm quality with potential biological reproductive implications both for basic research and in assisted reproduction techniques.
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- 2020
15. Peritoneal fluid from women with endometriosis impairs human spermatozoa functionality
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Sáez-Espinosa P, Velasco I, Lorca P, Acién MI, Romero A, and Gómez-Torres MJ
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Infertility ,Endometriosis ,Spermatozoa quality ,Peritoneal fluid - Abstract
The success of mammalian fertilization depends largely on spermatozoa physiological events. However, the manner in which endometriosis influence morpho-functional spermatozoa biomarkers is poorly defined. Here, we studied in vitro the effect of peritoneal fluid (PF) from women with endometriosis (PFE) and non-endometriosis (PFNE) on spermatozoa parameters. This research was prospective and double-blind. A total of 45 PF samples were collected from women with (n = 25) and without endometriosis (n = 20). Semen samples were obtained from normozoospermic donors (n = 15) and cultured with 20 % (v/v) of PF or commercial culture medium (controls) during 0, 24, and 48 h. The outcome measures were spermatozoa/viability, motility, tyrosine phosphorylation (TP) and spontaneous acrosomal reaction. In addition, plasma membrane sugars were characterized by lectins [Aleuria aurantia agglutinin (AAA), Concanavalin A (ConA), Peanut agglutinin (PNA), and Wheat germ agglutinin (WGA)]. After a 24-h culture, results reported a significant decrease in motility in cells cultured with PFE compared to the control, together with differences in the AAA and WGA-binding sites. Moreover, spermatozoa in contact with PFNE presented a significantly lower level of acrosome spontaneous reaction. At 48 h, no differences were observed in the biomarkers studied between the PFNE and the control, excluding ConA-binding sites. On the other hand, cells cultured with PFE exhibited significantly less motility, TP, and differences in the relocation of spermatozoa surface sugars. Viability was not affected in any culture condition. Overall, the effects of PFE could negatively affect spermatozoa quality, contributing to explain and diagnose the infertility associated to male partners of women with endometriosis.
- Published
- 2020
16. Risk factors associated with adverse events in neonates with peripherally inserted central catheter
- Author
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Padilla-Sanchez, C, Montejano-Lozoya, R, Benavent-Taengua, L, Monedero-Valero, A, Borras-Vano, MJ, Angel-Selfa, MJ, and Riera-Torres, MJ
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Adverse effects, Catéter venoso central de inserción periférica, Eventos adversos, Neonatal intensive care unit, Newborn, Peripherally inserted central catheter, Recién nacido, Unidad de cuidados intensivos neonatales - Abstract
Peripherally inserted central catheters have become a priority in infants who require long-term intravenous therapy, but their use involves certain risks.
- Published
- 2019
17. 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.
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- 2017
18. Response to Ebo et al., Letter to the Editor Regarding Update on Quinolone Allergy
- Author
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Doña I, Moreno, E, Perez-Sanchez, N, Andreu, I, Fernandez de Rojas DH, and Torres, MJ
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FLUOROQUINOLONE ,IGE ,BASOPHIL ACTIVATION TEST ,HYPERSENSITIVITY REACTIONS ,DIAGNOSIS ,AMOXICILLIN - Published
- 2017
19. Allergic Reactions to Metamizole: Immediate and Delayed Responses
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Blanca-López N, Pérez-Sánchez N, Agúndez JA, García-Martin E, Torres MJ, Cornejo-García JA, Perkins JR, Miranda MA, Andreu I, Mayorga C, Canto G, Blanca M, and Doña I
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Metamizole ,Skin test ,Basophil activation test ,Drug provocation test ,Selective hypersensitivity - Abstract
Background: Pyrazolones are the most common causes of selective nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We studied a large group of patients with immediate and delayed selective responses to metamizole. Methods: Patients with suspicion of hypersensitivity to metamizole were evaluated. We verified acetylsalicylic acid tolerance and classified patients as immediate or delayed responders if they showed symptoms less or more than 24 h after metamizole administration. Skin tests were performed and if negative, a basophil activation test (BAT) was performed on immediate responders. If it was negative, we performed a drug provocation test (DPT) with metamizole. Results: A total of 137 patients were included: 132 reacted within 24 h (single NSAID-induced urticaria/angioedema/anaphylaxis; SNIUAA) and 5 after 24 h (single NSAID-induced delayed hypersensitivity reaction; SNIDHR). Most SNIUAA patients developed anaphylaxis (60.60%); for SNIDHR, maculopapular exanthema was the most frequent entity (60%). Skin testing was positive in 62.04% of all cases and BAT in 28% of the SNIUAA patients with negative skin tests. In 5.1% of the cases, DPT with metamizole was needed to establish the diagnosis. In 22.62% of the cases, diagnosis was established by consistent and unequivocal history of repeated allergic episodes in spite of a negative skin test and BAT. Conclusions: SNIUAA to metamizole is the most frequent type of selective NSAID hypersensitivity, with anaphylaxis being the most common clinical entity. It may occur within 1 h after drug intake. SNIDHR occurs in a very low percentage of cases. The low sensitivity of diagnostic tests may be due to incomplete characterization of the chemical structures of metamizole and its metabolites. (C) 2016 S. Karger AG, Basel
- Published
- 2016
20. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole
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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
- 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-acetylaminoantipyrine (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
21. Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
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Violeta Gil-Ocaña, Isabel M. Jimenez, Cristobalina Mayorga, Inmaculada Doña, Jose Antonio Céspedes, Maria I. Montañez, Yolanda Vida, Maria J. Torres, Ezequiel Perez-Inestrosa, [Gil-Ocaña,V, Vida,Y, Perez-Inestrosa,E] Universidad de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Dpto. Química Orgánica, Málaga, Spain. [Gil-Ocaña,V, Mayorga,C, Montañez,MI, Torres,MJ, Perez-Inestrosa,E] Centro Andaluz de Nanomedicina y Biotecnología-BIONAND, Parque Tecnológico de Andalucía, Málaga, Spain. [Jimenez,IM, Doña,I, Céspedes,JA., Torres,MJ] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Jimenez,IM, Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Universidad de Málaga-Instituto de Investigación Biomédica de Málaga (IBIMA), Dpto. Medicina, Málaga, Spain., and This work was supported by the Spanish Ministerio de Ciencia e Innovación (Proyectos de I+D+I «Programación Conjunta Internacional», EuroNanoMed 2019 (PCI2019-111825-2), Ministerio de Ciencia y Educación (PID2019-104293GB-I00), Instituto de Salud Carlos III (ISCIII) of MINECO (grants cofunded by ERDF: ‘‘Una manera de hacer Europa’’ (Euronanomed Program AC19/00082, PI20/01734, PI18/00095, RETIC ARADYAL, RD16/0006/0001 and RD16/0006/0012, and Miguel Servet II program (CPII20/00028)), Junta de Andalucía and Universidad de Málaga (UMA18-FEDERJA-007), Andalusian Regional Ministry of Health (PE-0172-2018) and Nicolas Monardes Program (RC-0004-2021).
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Male ,Chemicals and Drugs::Biological Factors:: [Medical Subject Headings] ,silica nanoparticles ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Fertility Agents::Fertility Agents, Female [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Persons::Persons::Men::Nurses, Male [Medical Subject Headings] ,Immunology and Allergy ,Biepitope nanocomposites ,Aprobación de pruebas de diagnóstico ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings] ,Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Original Research ,Penicilinas ,Diagnostic test ,Middle Aged ,Silicon Dioxide ,Silica nanoparticles ,Specific IgE ,diagnostic test ,penicillins ,Female ,Hipersensibilidad a las drogas ,Persons::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings] ,Adult ,Dendrimers ,Adolescent ,Dendrimeric antigen ,Immunology ,specific IgE ,Chemicals and Drugs::Inorganic Chemicals::Silicon Compounds::Silicon Dioxide [Medical Subject Headings] ,Penicillins ,Chemicals and Drugs::Inorganic Chemicals::Minerals::Silicon Dioxide [Medical Subject Headings] ,Persons::Persons::Age Groups::Adolescent [Medical Subject Headings] ,Young Adult ,Humans ,Antigens ,Persons::Persons::Age Groups::Adult [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Antigens [Medical Subject Headings] ,Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [Medical Subject Headings] ,Aged ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Drug allergy ,Immunoglobulin E ,RC581-607 ,dendrimeric antigen ,biepitope nanocomposites ,Nanoparticles ,Immunologic diseases. Allergy ,Chemicals and Drugs::Macromolecular Substances::Polymers::Dendrimers [Medical Subject Headings] ,drug allergy - Abstract
β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic–inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.
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- 2021
22. Editorial: Drug Hypersensitivity: From Mechanisms to Improved Diagnosis and Standards of Care
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T. D. Fernandez, M. J. Torres, A. Romano, [Fernandez,TD, and Torres,MJ] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Fernandez,TD] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga-IBIMA, Málaga, Spain. [Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Departamento de Medicina, Universidad de Málaga-IBIMA, Málaga, Spain. [Torres,MJ] Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [Romano,A] IRCCS Oasi Maria S.S., Troina, Italy. [Romano,A] Fondazione Mediterranea G.B. Morgagni, Catania, Italy.
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Hipersensibilidad ,Drug ,medicine.medical_specialty ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions [Medical Subject Headings] ,diagnosis ,media_common.quotation_subject ,adverse reaction ,Disciplines and Occupations::Health Occupations::Medicine::Allergy and Immunology::Immunochemistry [Medical Subject Headings] ,RM1-950 ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,medicine ,Pharmacology (medical) ,Intensive care medicine ,Adverse effect ,media_common ,Pharmacology ,ComputingMilieux_THECOMPUTINGPROFESSION ,business.industry ,Diagnóstico ,Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals::Hospitals, General [Medical Subject Headings] ,drug ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings] ,TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,Preparaciones farmacéuticas ,Therapeutics. Pharmacology ,hypersensitivity ,business ,management - Abstract
Yes
- Published
- 2021
23. New Insights in Therapy for Food Allergy
- Author
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Mayorga, Cristobalina, Palomares, Francisca, Cañas, José A., Pérez-Sánchez, Natalia, Núñez, Rafael, Torres, María José, Gómez, Francisca, [Mayorga,C, Palomares,F, Cañas,JA, Núñez,R] Allergy Research Group, Instituto de Investigación Biomédica de Málaga (IBIMA),Málaga, Spain. [Mayorga,C, Pérez-Sánchez,N, Torres,MJ, Gomez,F] Allergy Clinical Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Medicine Department, Universidad de Málaga-UMA, Málaga, Spain., This research was funded by grants from the Institute of Health 'Carlos III' (ISCIII) of the Ministry of Economy and Competitiveness: PI17/01318 and PI18/00288. RETICS ARADyAL (RD16/0006/0001) and Sara Borrell (CD20/00085) Program. Andalusian Regional Ministry of Health (PE-0039-2018, and RH-0085-2020 and PI-0099-2020), Senior Clinical Researcher Program (B-0005-2019), and Nicolas Monardes Program (RC-0004-2021). Roche Pharma S.A. 'Stop Fuga de Cerebros' Program (SFC-0002-2020). Grants were co-funded by the European Regional Development Fund (ERDF). 'Una manera de hacer Europa' 'Andalucía se mueve con Europa'.
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Microbiota ,Specific immunotherapy ,Nanopartículas ,Non-specific therapy ,Hypoallergens ,Chemicals and Drugs::Complex Mixtures::Biological Products [Medical Subject Headings] ,Hipersensibilidad a los alimentos ,Phenomena and Processes::Microbiological Phenomena::Microbiota [Medical Subject Headings] ,Food allergy ,Nanoparticles ,Inmunoterapia ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Food Hypersensitivity [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings] ,Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [Medical Subject Headings] - Abstract
Food allergy is an increasing problem worldwide, with strict avoidance being classically the only available reliable treatment. The main objective of this review is to cover the latest information about the tools available for the diagnosis and treatment of food allergies. In recent years, many efforts have been made to better understand the humoral and cellular mechanisms involved in food allergy and to improve the strategies for diagnosis and treatment. This review illustrates IgE-mediated food hypersensitivity and provides a current description of the diagnostic strategies and advances in different treatments. Specific immunotherapy, including different routes of administration and new therapeutic approaches, such as hypoallergens and nanoparticles, are discussed in detail. Other treatments, such as biologics and microbiota, are also described. Therefore, we conclude that although important efforts have been made in improving therapies for food allergies, including innovative approaches mainly focusing on efficacy and safety, there is an urgent need to develop a set of basic and clinical results to help in the diagnosis and treatment of food allergies. Yes
- Published
- 2021
24. Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug-Induced Acute Urticaria/Angioedema
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Raquel Jurado-Escobar, Inmaculada Doña, José Triano-Cornejo, James R. Perkins, Natalia Pérez-Sánchez, Almudena Testera-Montes, Marina Labella, Joan Bartra, José J. Laguna, Miguel Estravís, José A. G. Agúndez, María J. Torres, José A. Cornejo-García, [Jurado-Escobar,R, Doña,I, Triano-Cornejo,J, Torres,MJ, Cornejo-García,JA] Allergy Research Group, Instituto De Investigación Biomédica De Málaga-IBIMA, Malaga, Spain. [Jurado-Escobar,R, Torres,MJ] Departamento De Medicina, Universidad De Málaga, Malaga, Spain. [Doña,I, Pérez-Sánchez,N, Testera-Montes,A, Labella,M, Torres,MJ] Allergy Unit, Hospital Regional Universitario De Málaga, Malaga, Spain. [Doña,I, Bartra,J, Laguna,JJ, Estravis,M, Agúndez,JAG, Cornejo-García,JA] ARADyAL Network, Instituto De Salud Carlos III, Madrid, Spain. [Perkins,JR] Department of Molecular Biology and Biochemistry, University of Malaga, Malaga, Spain. [Perkins,JR] CIBER De Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain. [Perkins,JR] The Biomedical Research Institute of Malaga (IBIMA), Malaga, Spain. [Bartra,J] Allergy Section, Pneumology Department, Hospital Clinic, Universitat De Barcelona, Barcelona, Spain. [Laguna,JJ] Allergy Unit, Allergo-Anaesthesia Unit, Hospital Central De La Cruz Roja, Faculty of Medicine, Alfonso X El Sabio University, Madrid, Spain. [Estravis,M] Instituto De Investigación Biomédica De Salamanca (IBSAL), Salamanca, Spain. [Agúndez,JAG] Institute of Molecular Pathology Biomarkers, UEx, Cáceres, Spain. [Torres,MJ] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Malaga, Spain., and This work was supported by Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Science and Innovation), co-founded by Fondo Europeo de Desarrollo Regional-FEDER for Research Projects (PI17/ 01593, PI18/00540, and PI20/01540), GR18145 from Junta de Extremadura, the Thematic Networks and Co-operative Research
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0301 basic medicine ,Polimorfismo Genético ,Single-nucleotide polymorphism ,RM1-950 ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic Agents [Medical Subject Headings] ,03 medical and health sciences ,0302 clinical medicine ,Phospholipase A2 ,Cytosolic phospholipase A2 ,Genetic variation ,arachidomic acid ,medicine ,Pharmacology (medical) ,Phenomena and Processes::Chemical Phenomena::Chemical Processes::Hydrolysis [Medical Subject Headings] ,cytosolic phospholipase A2 ,skin and connective tissue diseases ,Gene ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Phospholipases::Phospholipases A::Phospholipases A2 [Medical Subject Headings] ,Ácido araquidónico ,Original Research ,Pharmacology ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,biology ,Angioedema ,business.industry ,urticaria/angioedema ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids::Arachidonic Acid [Medical Subject Headings] ,Diseases::Cardiovascular Diseases::Vascular Diseases::Angioedema [Medical Subject Headings] ,Angioneurotic oedema ,NSAID cross-hypersensitivity ,PLA2G4A ,030104 developmental biology ,Arachidomic acid ,030220 oncology & carcinogenesis ,Immunology ,Fosfolipasas A2 grupo IV ,biology.protein ,Cyclooxygenase ,Therapeutics. Pharmacology ,medicine.symptom ,Urticaria/angioedema ,business ,polymorphisms ,Polymorphisms - Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity reactions, probably due to their high consumption worldwide. The most frequent type of NSAID hypersensitivity is NSAID cross-hypersensitivity, in which patients react to NSAIDs from different chemical groups in the absence of a specific immunological response. The underlying mechanism of NSAID cross-hypersensitivity has been linked to cyclooxygenase (COX)-1 inhibition causing an imbalance in the arachidonic acid pathway. Despite NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype, most studies have focused on NSAID-exacerbated respiratory disease. As NSAID cross-hypersensitivity reactions are idiosyncratic, only appearing in some subjects, it is believed that individual susceptibility is under the influence of genetic factors. Although associations with polymorphisms in genes from the AA pathway have been described, no previous study has evaluated the potential role of cytosolic phospholipase A2 (cPLA2) variants. This enzyme catalyzes the initial hydrolysis of membrane phospholipids to release AA, which can be subsequently metabolized into eicosanoids. Here, we analyzed for the first time the overall genetic variation in the cPLA2 gene (PLA2G4A) in NIUA patients. For this purpose, a set of tagging single nucleotide polymorphisms (tagSNPs) in PLA2G4A were selected using data from Europeans subjects in the 1,000 Genomes Project, and genotyped with the iPlex Sequenom MassArray technology. Two independent populations, each comprising NIUA patients and NSAID-tolerant controls, were recruited in Spain, for the purposes of discovery and replication, comprising a total of 1,128 individuals. Fifty-eight tagSNPs were successfully genotyped in the discovery cohort, of which four were significantly associated with NIUA after Bonferroni correction (rs2049963, rs2064471, rs12088010, and rs12746200). These polymorphisms were then genotyped in the replication cohort: rs2049963 was associated with increased risk for NIUA after Bonferroni correction under the dominant and additive models, whereas rs12088010 and rs12746200 were protective under these two inheritance models. Our results suggest a role for PLA2G4A polymorphisms in NIUA. However, further studies are required to replicate our findings, elucidate the mechanistic role, and evaluate the participation of PLA2G4A variants in other phenotypes induced by NSAID cross-hypersensitivity.
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- 2021
25. The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
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Cristobalina Mayorga, Maria I. Montañez, Francisco Najera, Gador Bogas, Tahía D. Fernandez, David Rodríguez Gil, Ricardo Palacios, Maria J. Torres, Yolanda Vida, Ezequiel Perez-Inestrosa, [Mayorga,C, Montañez,MI, Bogas,G, Fernandez,TD, Torres,MJ] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Mayorga,C, Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Mayorga,C, Najera,F, Torres,MJ, Vida,Y, Perez-Inestrosa,E] Centro Andaluz de Nanomedicina y Biotecnología-BIONAND, Parque Tecnológico de Andalucía, Málaga, Spain. [Najera,F, Perez-Inestrosa,E] Universidad de Málaga-IBIMA Departamento de Química Orgánica, Málaga, Spain. [Fernandez,TD] Universidad de Málaga-IBIMA, Departamento de Biología celular, Genética y Fisiología, Málaga, Spain. [Gil,DR, Palacios,R] Diater Laboratorios S.A., Madrid, Spain. [Torres,MJ] Universidad de Málaga-IBIMA, Departamento de Medicina, Málaga, Spain., and This work was supported by the Spanish Ministerio de Economía, Industria y Competitividad (CTQ2016-75870-P), Ministerio de Ciencia y Educación (PID2019-104293GB-I00), Ministerio de Ciencia e Innovación (Proyectos de I + D + I « Programación Conjunta Internacional», EuroNanoMed 2019 (PCI2019-111825-2), Instituto de Salud Carlos III (ISCIII) of MINECO (grants cofunded by ERDF:'Una manera de hacer Europa' (PI17/01237, PI18/00095, RETIC ARADYAL, RD16/0006/0001and RD16/0006/0012, Euronanomed Program AC19/00082, 'Joan Rodés' program (JR18/00054) and Miguel Servet I program (CP15/00103), Junta de Andalucía and Universidad de Málaga (UMA18-FEDERJA-007), Andalusian Regional Ministry of Health (PI-0179-2014, PE-0172-2018) and Nicolas Monardes Program (RC-0004-2016C) and 'Premio UNICAJA a la innovación en biomedicina y salud'.
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0301 basic medicine ,Provocation test ,antigenic determinant ,Antigenic determinant ,Immunoglobulin E ,Benzylpenicillin ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Pharmacology (medical) ,Hipersensibilidad medicamentosa ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings] ,Original Research ,Epítopos ,media_common ,biology ,Chemistry ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Tests, Routine [Medical Subject Headings] ,Penicilinas ,Diagnostic test ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings] ,Specific IgE ,Inmunoglobulina E ,Biochemistry ,diagnostic test ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings] ,medicine.drug ,Drug ,media_common.quotation_subject ,Drug allergy ,specific IgE ,Diseases::Immune System Diseases::Hypersensitivity [Medical Subject Headings] ,03 medical and health sciences ,In vivo ,medicine ,Pharmacology ,lcsh:RM1-950 ,Pruebas diagnósticas rutinarias ,Penicillin ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins [Medical Subject Headings] ,Chemicals and Drugs::Macromolecular Substances::Polymers [Medical Subject Headings] ,medicine.disease ,In vitro ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Weights and Measures::Reference Standards [Medical Subject Headings] ,penicillin ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030228 respiratory system ,Chemicals and Drugs::Organic Chemicals::Amines::Butylamines [Medical Subject Headings] ,Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings] ,biology.protein ,drug allergy - Abstract
The high prevalence of allergy to β-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated in vivo method for diagnosing immediate reactions to β-lactams. Although drug provocation test is the reference standard, it cannot be performed in highly risk reactions or in those with positive skin tests. For skin tests, the inclusion of major and minor determinants of benzylpenicillin (BP) is recommended. Commercial skin test reagents have changed along time, including as minor determinants benzylpenicillin, benzylpenicilloate (BPO), and benzylpenilloate (PO). Major determinants consists of multivalent conjugates of benzylpenicilloyl coupled through amide bond to a carrier polymer, such as penicilloyl-polylysine (PPL) or benzylpenicilloyl-octalysine (BP-OL). The chemical stability of such reagents has influenced the evolution of the composition of the commercial kits, as this requirement is necessary for improving the quality and standardization of the product. In this work, we provide a detailed study of the chemical stability of BP determinants. We observed that those structures suffer from an epimerization process in C-5 at different rates. Butylamine-Benzylpenicilloyl conjugates (5R,6R)-Bu-BPO and (5S,6R)-Bu-BPO were selected as a simple model for mayor determinant to evaluate the role of the different epimers in the immunoreactivity with sera from penicillin-allergic patients. In vitro immunoassays indicate that any change in the chemical structure of the antigenic determinant of BP significantly affects IgE recognition. The inclusion of stereochemically pure compounds or mixtures may have important implications for both the reproducibility and sensitivity of in vivo and in vitro diagnostic tests.
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- 2021
26. Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes
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Maria Salas, Isabel M. Jiménez-Sánchez, Angela Martin-Serrano, Gador Bogas, Maria I. Montañez, Esther Barrionuevo, Cristobalina Mayorga, Teresa Posadas, María José Torres, Ruben Fernandez-Santamaria, Tahia D. Fernandez, Adriana Ariza, [Bogas,G, Mayorga,G, Martín-Serrano,A, Fernández-Santamaría,R, Jiménez-Sánchez,IM, Ariza,A, Barrionuevo,E, Posadas,T, Salas,M, Fernández,TD, Torres,MJ, Montañez,MI] Allergy Research Group, Instituto de Investigación Biomédica de Málaga- IBIMA, Hospital Civil, Málaga, Spain. [Bogas,G, Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Hospital Civil, Málaga, Spain. [Mayorga,G, Montañez,MI] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [Fernández,TD] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Málaga, Spain. [Torres,MJ] Departamento de Medicina, Universidad de Málaga, Facultad de Medicina, Málaga, Spain., The present study has been supported by the Institute of Health ‘‘Carlos III’’ (ISCIII) of MINECO (Grants cofunded by ERDF: ‘‘Una manera de hacer Europa’’: Grant ns. PI12/02529, PI15/01206, CP15/00103, PI17/01237, PI18/00095, RETIC ARADYAL RD16/0006/0001, Euronanomed Program AC19/00082, Andalusian Regional Ministry of Economy and Knowledge (Grants cofunded by ERDF: ‘‘Andalucía se mueve con Europa’’: Grant No. CTS-06603), Andalusian Regional Ministry of Health (Grant Nos. PI-0699–2011, PI-0179–2014, PE-0172–2018 cofunded by ERDF), and and ‘‘Premio UNICAJA a la innovación en biomedicina y salud.’’ C.M. holds ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health (Grant No. C-0044–2012 SAS2013). G.B. holds a 'Juan Rodes' Grant (JR18/00054), M.I.M. holds a ‘‘Miguel Servet I’’ Grant (CP15/00103), and A.A. holds a ‘‘Sara Borrell’’ Grant (CD17/0146), all by ISCIII of MINECO (grants cofunded by European Social Fund: ‘‘El FSE invierte en futuro’’). R.F.S. holds a predoctoral Grant (PE-0172–2018) cofunded by ERDF.
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Pulmonary and Respiratory Medicine ,medicine.drug_class ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings] ,Immunology ,Cephalosporin ,Phenomena and Processes::Immune System Phenomena::Immune System Processes::Antigen-Antibody Reactions::Cross Reactions [Medical Subject Headings] ,Cefalosporinas ,Antigenic determinant ,Pharmacology ,medicine.disease_cause ,Benzylpenicillin ,Group A ,Cross-reactivity ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,03 medical and health sciences ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin [Medical Subject Headings] ,0302 clinical medicine ,Reacciones cruzadas ,medicine ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams [Medical Subject Headings] ,Immunology and Allergy ,030304 developmental biology ,Amoxicilina ,Epítopos ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Radioallergosorbent test ,Research ,Amoxicillin ,Betalactam ,Drug allergy ,Beta-lactamas ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Cephalosporins [Medical Subject Headings] ,Penicillin ,Specific IgE ,030228 respiratory system ,Inmunoglobulina E ,Cefadroxil ,Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity [Medical Subject Headings] ,Hipersensibilidad a las Drogas ,business ,Cefuroxime ,medicine.drug - Abstract
Background Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods Fifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results Tolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions Cross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients. Background Betalactams (BLs) are the drugs most frequently involved in immediate (IgE-mediated) hypersensitivity reactions (IHRs) [1,2,3], which could be explained by their ability to act as haptens due to their high chemical reactivity against proteins [4, 5]. BL chemical structure is formed by a 4-membered ring (the so-called BL ring) that in penicillins is fused to a 5-membered thiazolidine ring, and in cephalosporins to a 6-membered dihydrothiazine ring (Fig. 1). These drugs have a side chain (R1) bound to the BL ring; besides, cephalosporins have a second side chain (R2) bound to the dihydrothiazine ring, whose chemical structures distinguish the different compounds [6, 7]. Yes
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- 2020
27. Precision Medicine in House Dust Mite-Driven Allergic Asthma
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Eguiluz-Gracia, Ibon, Palomares, Francisca, Salas, Maria, Testera-Montes, Almudena, Ariza, Adriana, Davila, Ignacio, Bartra, Joan, Mayorga, Cristobalina, Torres, Maria Jose, Rondon, Carmen, [Eguiluz-Gracia,I, Salas,M, Testera-Montes,A, Mayorga,C, Torres,MJ, Rondon,C] Allergy Unit, Hospital Regional Universitario de Malaga, Malaga, Spain. [Eguiluz-Gracia,I, Palomares,F, Ariza,A, Rondon,C] Allergy Research Group, Instituto de Investigación Biomedica de Malaga-IBIMA and ARADyAL, Malaga, Spain. [Testera-Montes,A, Torres,MJ] Department of Medicine and Dermatology, Universidad de Malaga, Malaga, Spain. [Davila,I] Allergy Department, University Hospital of Salamanca, Salamanca, Spain. [Davila,I] Allergy Research Group, Institute for Biomedical Research of Salamanca (IBSAL) and ARADyAL, Salamanca, Spain. [Davila,I] Department of Biomedical and Diagnostic Sciences, Universidad de Salamanca, Salamanca, Spain. [Bartra,J] Allergy Section, Pulmonology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain. [Bartra,J] Clinical & Experimental Respiratory Immunoallergy (IRCE), Instituto de Investigaciones Biomedicas Pi I Sunyer (IDIBAPS)-ARADyAL, Barcelona, Spain. [Mayorga,C, Torres,MJ] Laboratory for Nanostructures for the Diagnosis and Treatment of Allergic Diseases, Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Malaga, Spain., and This work was supported by the Instituto de Salud Carlos III of the Spanish Ministry of Science and Competitiveness (grants co-funded by the European Regional Development Fund) through the research contracts 'Rio Hortega' for ATM (CM20/00160), 'Juan Rodes' for IEG (JR19/00029) and 'Sara Borrell' for AA (CD17/00146), the research project PI17/01410 and the program of Redes Temáticas de Investigación Colaborativa en Salud (RETICS): Asma, Reacciones Adversas y Alérgicas-ARADyAL (RD16/0006/0001, RD16/0006/0007, RD16/0006/0019 and RD16/0006/0021). This work was also supported by the Andalusian Regional Ministry of Health through the 'Nicolas Monardes' program for CM (RC-0004-2016C).
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Chemicals and Drugs::Pharmaceutical Preparations::Dosage Forms::Tablets [Medical Subject Headings] ,Antígenos dermatofagoides ,Sublingual allergen immunotherapy ,Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,House dust mites ,Pyroglyphidae ,Organisms::Eukaryota::Animals::Invertebrates::Arthropods::Arachnida::Acari::Mites::Pyroglyphidae [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Respiratory System::Respiratory Function Tests::Bronchial Provocation Tests [Medical Subject Headings] ,Allergic asthma ,Pruebas de provocación bronquial ,Inmunoterapia sublingual ,Hipersensibilidad respiratoria ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Desensitization, Immunologic::Sublingual Immunotherapy [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Local allergic asthma ,Diseases::Respiratory Tract Diseases::Respiratory Hypersensitivity::Asthma [Medical Subject Headings] ,Diseases::Respiratory Tract Diseases::Respiratory Hypersensitivity [Medical Subject Headings] ,Bronchial allergen challenge ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Dermatophagoides [Medical Subject Headings] - Abstract
House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA. Yes
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- 2020
28. Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs
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Raquel Jurado-Escobar, Inmaculada Doña, Gador Bogas-Herrera, Natalia Pérez-Sánchez, María Salas, José J. Laguna, Rosa Muñoz-Cano, Cristobalina Mayorga, María J. Torres, José A. Cornejo-García, [Jurado-Escobar,R, Doña,I, Mayorga,C, Torres,MJ, Cornejo-García,JA] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain. [Jurado-Escobar,R, Torres,MJ] Departamento de Medicina, Universidad de Málaga, Malaga, Spain. [Doña,I, Bogas-Herrera,G, Pérez-Sánchez,N, Salas,M, Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Malaga, Spain. [Doña,I, Laguna,JJ, Muñoz-Cano,R, Cornejo-García,JA] ARADyAL Network, Instituto de Salud Carlos III, Madrid, Spain. [Laguna,JJ] Allergy Unit, Allergo-Anaesthesia Unit, Hospital Central de la Cruz Roja, Faculty of Medicine, Alfonso X El Sabio University, Madrid, Spain. [Muñoz-Cano,R] Allergy Section, Pneumology Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain. [Mayorga,C, 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 Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Science and Innovation) co-founded by Fondo Europeo de Desarrollo Regional-FEDER for Research Projects (PI17/01,593), the Thematic Networks and Cooperative Research Centers: ARADyAL RD16/0006/0001, 0007, and 0033, and from the Sociedad Española de Alergología e Inmunología Clínica (SEAIC, and Ref. Convocatoria Ayudas 2016 and Convocatoria Ayudas 2018 Ref. 18 B02).
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0301 basic medicine ,Hipersensibilidad ,Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,Urticaria ,NSAIDs ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,transcellular metabolism ,0302 clinical medicine ,Chemicals and Drugs::Biological Factors::Inflammation Mediators::Autacoids::Eicosanoids::Leukotrienes [Medical Subject Headings] ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Monocytes [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Integrins [Medical Subject Headings] ,Medicine ,Pharmacology (medical) ,Platelet ,Original Research ,biology ,Anatomy::Cells::Blood Cells::Leukocytes::Granulocytes::Eosinophils [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Eicosanoids::Arachidonic Acids::Leukotrienes::SRS-A::Leukotriene E4 [Medical Subject Headings] ,Integrinas ,Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Granulocytes::Neutrophils [Medical Subject Headings] ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,Integrin alpha M ,medicine.symptom ,CD61 ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases::Cyclooxygenase 1 [Medical Subject Headings] ,Integrin ,CD11c ,CD18 ,CD11a ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents [Medical Subject Headings] ,03 medical and health sciences ,cysteinyl-leukotrienes ,platelet-adherent leukocytes ,Hypersensitivity ,Pharmacology ,Angioedema ,business.industry ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal [Medical Subject Headings] ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Diseases, Vascular::Urticaria [Medical Subject Headings] ,lcsh:RM1-950 ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids::Arachidonic Acid [Medical Subject Headings] ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030228 respiratory system ,Immunology ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Sulfur::Cysteine [Medical Subject Headings] ,biology.protein ,integrins ,nonsteroidal anti-inflammatory drugs-hypersensitivity ,business ,Antiinflamatorios no esteroideos - Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most highly consumed drugs worldwide and the main triggers of drug hypersensitivity reactions. The most frequent reaction, named cross-reactive NSAID-hypersensitivity, is due to the pharmacological activity of these drugs by blocking the cyclooxygenase-1 enzyme. Such inhibition leads to cysteinyl-leukotriene synthesis, mainly LTE4, which are responsible for the reaction. Although the complete molecular picture of the underlying mechanisms remains elusive, the participation of platelet-adherent leukocytes (CD61+) and integrins have been described for NSAID-exacerbated respiratory disease (NERD). However, there is a lack of information concerning NSAID-induced urticaria/angioedema (NIUA), by far the most frequent clinical phenotype. Here we have evaluated the potential role of CD61+ leukocytes and integrins (CD18, CD11a, CD11b, and CD11c) in patients with NIUA, and included the other two phenotypes with cutaneous involvement, NSAID-exacerbated cutaneous disease (NECD) and blended reactions (simultaneous skin and airways involvement). A group NSAID-tolerant individuals was also included. During the acute phase of the reaction, the three clinical phenotypes showed increased frequencies of CD61+ neutrophils, eosinophils, and monocytes compared to controls, which correlated with urinary LTE4 levels. However, no correlation was found between these variables at basal state. Furthermore, increased expressions of CD18 and CD11a were found in the three CD61+ leukocytes subsets in NIUA, NECD and blended reactions during the acute phase when compared with CD61−leukocyte subpopulations. During the acute phase, CD61+ neutrophils, eosinophils and monocytes showed increased CD18 and CD11a expression when compared with CD61+ leukocytes at basal state. No differences were found when comparing controls and CD61+ leukocytes at basal state. Our results support the participation of platelet-adherent leukocytes and integrins in cutaneous cross-hypersensitivity to NSAIDs and provide a link between these cells and arachidonic acid metabolism. Our findings also suggest that these reactions do not involve a systemic imbalance in the frequency of CD61+ cells/integrin expression or levels of LTE4, which represents a substantial difference to NERD. Although further studies are needed, our results shed light on the molecular basis of cutaneous cross-reactive NSAID-hypersensitivity, providing potential targets for therapy through the inhibition of platelet-leukocyte interactions.
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- 2020
29. Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies
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Ángela Martín-Serrano, Juan M. Gonzalez-Morena, Nekane Barbero, Adriana Ariza, Francisco J. Sánchez Gómez, Ezequiel Pérez-Inestrosa, Dolores Pérez-Sala, Maria J. Torres, María I. Montañez, [Martín-Serrano,A, Ariza,A, Torres,MJ, Montañez,MI] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Martín-Serrano.A, Barbero,N, Pérez-Inestrosa,E, Montañez,MI] Centro Andaluz de Nanomedicina y Biotecnología-BIONAND, Málaga, Spain. [Gonzalez-Morena,JM] Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain. [Barbero,N, Pérez-Inestrosa,E] Department Química Orgánica, Universidad de Málaga-IBIMA, Málaga, Spain. [Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Málaga, Spain. [Torres,MJ] Department of Medicina, Universidad de Málaga, Málaga, Spain., Work at MJT and MIM laboratory was supported by Instituto de Salud Carlos III (ISCIII) of MICINN (grants cofunded by ERDF: 'Una manera de hacer Europa' (PI17/01237, PI18/00095, RETIC ARADYAL RD16/0006/0001 and Euronanomed Program AC19/ 00082), Miguel Servet I program (CP15/00103) and Sara Borrell program (CD17/00146)), Andalusian Regional Ministry of Health (PI-0179-2014, PE-0172-2018). Work at EP-I laboratory was supported by the Spanish Ministerio de Economía, Industria y Competitividad (CTQ 2016-75870-P), Ministerio de Ciencia y Educación (PID 2019-104293GB-I00), Ministerio de Ciencia e Innovación [Proyectos de I+D+I Programación Conjunta Internacional, EuroNanoMed 2019 (PCI 2019-111825-2)], ISCIII RETIC ARADYAL RD16/0006/0012 and Junta de Andalucía (UMA18-FEDERJA-007). Work at DP-S laboratory was supported by Grants from Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (MICINN, Spain) and European Regional Development Fund, SAF 2015-68590-R and RTI 2018-097624-B-I00, ISCIII RETIC ARADyAL RD16/0006/0021., Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Martín-Serrano, Ángela [0000-0002-2908-8910], González-Morena, Juan M. [0000-0003-2932-0756], Pérez-Inestrosa, Ezequiel [0000-0001-7546-5273], Pérez-Sala, Dolores [0000-0003-0600-665X], Montañez, M. I. [0000-0001-6641-5979], Torres, María J. [0000-0003-4499-840X], Martín-Serrano, Ángela, González-Morena, Juan M., Pérez-Inestrosa, Ezequiel, Pérez-Sala, Dolores, Montañez, M. I., and Torres, María J.
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0301 basic medicine ,Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Solubility [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Clavulanic Acids::Clavulanic Acid [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins [Medical Subject Headings] ,Peptide ,Biotina ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ácido clavulánico ,Biotin ,Peptide mass fingerprinting ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Imidazoles::Biotin [Medical Subject Headings] ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Biotinylation [Medical Subject Headings] ,medicine ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides [Medical Subject Headings] ,Pharmacology (medical) ,biotinylation ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Alpha-Globulins::Haptoglobins [Medical Subject Headings] ,Original Research ,chemistry.chemical_classification ,Pharmacology ,biology ,betalactam ,haptenation ,lcsh:RM1-950 ,Anatomy::Hemic and Immune Systems::Immune System [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Albumins::Ovalbumin::Avidin [Medical Subject Headings] ,Human serum albumin ,Beta-lactamas ,Blood proteins ,clavulanate ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,030228 respiratory system ,chemistry ,Biochemistry ,Biotinylation ,biology.protein ,Hipersensibilidad a las drogas ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings] ,Linker ,biotin tag ,drug allergy ,Avidin ,medicine.drug - Abstract
16 p.-6 fig., Clavulanic acid (CLV) and amoxicillin, frequently administered in combination, can be independently involved in allergic reactions. Protein haptenation with β-lactams is considered necessary to activate the immune system. The aim of this study was to assess the suitability of biotinylated analogues of CLV as probes to study protein haptenation by this β-lactam. Two synthetic approaches afforded the labeling of CLV through esterification of its carboxylic group with a biotin moiety, via either direct binding (CLV-B) or tetraethylenglycol linker (CLV-TEG-B). The second analogue offered advantages as solubility in aqueous solution and potential lower steric hindrance for both intended interactions, with the protein and with avidin. NMR reactivity studies showed that both CLV and CLV-TEG-B reacts through β-lactam ring opening by aliphatic amino nitrogen, however with different stability of resulting conjugates. Unlike CLV conjugates, that promoted the decomposition of clavulanate fragment, the conjugates obtained with the CLV-TEG-B remained linked, as a whole structure including biotin, to nucleophile and showed a better stability. This was a desired key feature to allow CLV-TEG-B conjugated protein detection at great sensitivity. We have used biotin detection and mass spectrometry (MS) to detect the haptenation of human serum albumin (HSA) and human serum proteins. MS of conjugates showed that HSA could be modified by CLV-TEG-B. Remarkably, HSA preincubation with CLV excess only reduced moderately the incorporation of CLV-TEG-B, which could be attributed to different protein interferences. The CLV-TEG-B fragment with opened β-lactam was detected bound to the 404–430HSA peptide of the treated protein. Incubation of human serum with CLV-TEG-B resulted in the haptenation of several proteins that were identified by 2D-electrophoresis and peptide mass fingerprinting as HSA, haptoglobin, and heavy and light chains of immunoglobulins. Taken together, our results show that tagged-CLV keeps some of the CLV features. Moreover, although we observe a different behavior in the conjugate stability and in the site of protein modification, the similar reactivity indicates that it could constitute a valuable tool to identify protein targets for haptenation by CLV with high sensitivity to get insights into the activation of the immune system by CLV and mechanisms involved in β-lactams allergy., Work at MJT and MIM laboratory was supported by Instituto de Salud Carlos III (ISCIII) of MICINN (grants cofunded by ERDF: “Una manera de hacer Europa” (PI17/01237, PI18/00095, RETIC ARADYAL RD16/0006/0001 and Euronanomed Program AC19/00082), Miguel Servet I program (CP15/00103) and Sara Borrell program (CD17/00146)), Andalusian Regional Ministry of Health (PI-0179-2014, PE-0172-2018). Work at EP-I laboratory was supported by the Spanish Ministerio de Economía, Industria y Competitividad (CTQ 2016-75870-P), Ministerio de Ciencia y Educación (PID 2019-104293GB-I00), Ministerio de Ciencia e Innovación [Proyectos de I+D+I Programación Conjunta Internacional, EuroNanoMed 2019 (PCI 2019-111825-2)], ISCIII RETIC ARADYAL RD16/0006/0012 and Junta de Andalucía (UMA18-FEDERJA-007). Work at DP-S laboratory was supported by Grants from Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (MICINN, Spain) and European Regional Development Fund, SAF 2015-68590-R and RTI 2018-097624-B-I00, ISCIII RETIC ARADyAL RD16/0006/0021.
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- 2020
30. Amoxicillin inactivation by thiol-catalyzed cyclization reduces protein haptenation and antibacterial potency
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María A. Pajares, Tahl Zimmerman, Francisco J. Sánchez-Gómez, Adriana Ariza, María J. Torres, Miguel Blanca, F. Javier Cañada, María I. Montañez, Dolores Pérez-Sala, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, European Commission, CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI), Pajares, María A., Zimmerman, T., Blanca, Miguel, Cañada, F. Javier, Montañez, M. I., Pérez-Sala, Dolores, Pajares, María A. [0000-0002-4714-9051], Zimmerman, T. [0000-0001-5939-6394], Blanca, Miguel [0000-0003-1631-4621], Cañada, F. Javier [0000-0003-4462-1469], Montañez, M. I. [0000-0001-6641-5979], Pérez-Sala, Dolores [0000-0003-0600-665X], [Pajares,MA, Zimmerman,T, Sánchez-Gómez,FJ, Cañada,FJ, Pérez-Sala,D] Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain. [Ariza,A, Torres,MJ, Montañez,MI] Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Civil, Málaga, Spain. [Ariza,A, Montañez,MI] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology- BIONAND, Málaga, Spain. [Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Hospital Civil, Málaga, Spain. [Blanca,M] Servicio de Alergología, Hospital Infanta Leonor, Madrid, Spain., This work was supported by grant SAF2015-68590-R from MINECO/FEDER, RTI2018-097624-B-I00 and RETIC Aradyal from ISCIII/FEDER RD16/0006/0021 to DP-S, RD16/0006/0001 to MT, RD16/0006/0024 to MB, and grants CP15/00103 and PI17/01237 from ISCIII/ERDF and PI-0179-2014 from Andalusian Regional Ministry Health to MM. AA holds a 'Sara Borrell' research contract (CD17/0146) supported by ISCIII from MINECO [confounded by the European Social Fund (ESF)]. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).
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0301 basic medicine ,Metabolite ,Antibiotics ,Crecimiento bacteriano ,Benzylpenicillin ,Dithiothreitol ,chemistry.chemical_compound ,0302 clinical medicine ,Chemicals and Drugs::Organic Chemicals::Alcohols::Sugar Alcohols::Dithiothreitol [Medical Subject Headings] ,Inactivation mechanism ,Ampicillin ,polycyclic compounds ,Pharmacology (medical) ,Protein adducts ,Thiol-containing molecules ,Amoxicilina ,Original Research ,Chemistry ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Cephalosporins::Cephalexin::Cefaclor [Medical Subject Headings] ,Beta-lactamas ,Human serum albumin ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Oligopeptides::Glutathione [Medical Subject Headings] ,B-lactam antibiotics ,Biochemistry ,030220 oncology & carcinogenesis ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings] ,medicine.drug ,Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Indicators and Reagents::Reducing Agents [Medical Subject Headings] ,medicine.drug_class ,Diseases::Immune System Diseases::Hypersensitivity [Medical Subject Headings] ,Phenomena and Processes::Chemical Phenomena::Chemical Processes::Physicochemical Processes::Oxidation-Reduction [Medical Subject Headings] ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Piperazines::Diketopiperazines [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin [Medical Subject Headings] ,03 medical and health sciences ,thiol-containing molecules ,β-lactam antibiotics ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams [Medical Subject Headings] ,medicine ,otorhinolaryngologic diseases ,Thiol groups ,Pharmacology ,Bacterial growth ,lcsh:RM1-950 ,Beta lactam antibiotic ,Amoxicillin ,Glutathione ,Metabolism ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Redox regulation ,Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Amino Acids, Sulfur::Cysteine::Acetylcysteine [Medical Subject Headings] - Abstract
16 p.-7 fig.-2 tab.-1 graph. abst., Serum and cellular proteins are targets for the formation of adducts with the β-lactam antibiotic amoxicillin. This process could be important for the development of adverse, and in particular, allergic reactions to this antibiotic. In studies exploring protein haptenation by amoxicillin, we observed that reducing agents influenced the extent of amoxicillin-protein adducts formation. Consequently, we show that several thiol-containing compounds, including dithiothreitol, N-acetyl-L-cysteine, and glutathione, perform a nucleophilic attack on the amoxicillin molecule that is followed by an internal rearrangement leading to amoxicillin diketopiperazine, a known amoxicillin metabolite with residual activity. Increased diketopiperazine conversion is also observed with human serum albumin but not with L-cysteine, which mainly forms the amoxicilloyl amide. The effect of thiols is catalytic and can render complete amoxicillin conversion. Interestingly, this process is dependent on the presence of an amino group in the antibiotic lateral chain, as in amoxicillin and ampicillin. Furthermore, it does not occur for other β-lactam antibiotics, including cefaclor or benzylpenicillin. Biological consequences of thiol-mediated amoxicillin transformation are exemplified by a reduced bacteriostatic action and a lower capacity of thiol-treated amoxicillin to form protein adducts. Finally, modulation of the intracellular redox status through inhibition of glutathione synthesis influenced the extent of amoxicillin adduct formation with cellular proteins. These results open novel perspectives for the understanding of amoxicillin metabolism and actions, including the formation of adducts involved in allergic reactions., This work was supported by grant SAF2015-68590-R from MINECO/FEDER, RTI2018-097624-B-I00 and RETIC Aradyal from ISCIII/FEDER RD16/0006/0021 to DP-S; RD16/0006/0001 to MT, RD16/0006/0024 to MB; grants CP15/00103 and PI17/ 01237 from ISCIII/ERDF and PI-0179-2014 from Andalusian Regional Ministry Health to MM. AA holds a “Sara Borrell” research contract (CD17/0146) supported by ISCIII from MINECO [confounded by the European Social Fund (ESF)]. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI)
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- 2020
31. 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).
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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
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- 2020
32. Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests
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Amene Tesfaye, Yolanda Vida, Noemi Molina, Angela Martin-Serrano, Ezequiel Perez-Inestrosa, María José Torres, Maria I. Montañez, Cristobalina Mayorga, Francisco Najera, Tahia D. Fernandez, [Molina,N, Najera,F, Vida,Y, Perez-Inestrosa,E] Departamento de Química Orgánica, Universidad de Málaga—IBIMA, Málaga, Spain. [Molina,N, Martin-Serrano,A, Fernandez,TD, Tesfaye,A, Torres,MJ, Mayorga,C, Montañez,MI, Perez-Inestrosa,E] Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnológico de Andalucía, Málaga, Spain. [Martin-Serrano,A, Fernandez,TD, Tesfaye,A, Montañez,MI] Research Laboratory, IBIMA—Regional University Hospital of Málaga—UMA, Málaga, Spain. [Torres,MJ, Mayorga,C] Allergy Unit, IBIMA—Regional University Hospital of Málaga—UMA,Málaga, Spain, The present study has been supported by State Secretariat for Research, Development and Innovation of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF)): MINECO CTQ2016-75870P, by Institute of Health 'Carlos III' (ISCIII) of MINECO (grants cofunded by ERDF): PI12/02529, PI15/01206, CP15/00103, PI17/01237, RETICs RIRAAF RD12/0013/0001 and 0003 and RETIC ARADYAL RD16/0006/0001 and 0012, by Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by ERDF): CTS-06603, and by Andalusian Regional Ministry Health (grants: PI-0699-2011, PI-0179-2014, PI-0241-2016 and PI-0250-2016), and 'Premio UNICAJA a la innovación en biomedicina y salud'. NM holds a FPU grant of MECD (FPU15/00641). TDF hold a 'Ramon y Cajal' research contract from MINECO (RYC-2013-13138). AT has received funding from the European Union’s H2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 713721. CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. MIM holds a 'Miguel Servet I' (CP15/00103) contract by ISCIII of MINECO (grants cofunded by European Social Fund (ESF)). Partially supported by Open Access Funds from 'Universidad de Málaga'.
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0301 basic medicine ,Models, Molecular ,Magnetic Resonance Spectroscopy ,Pharmaceutical Science ,Basophil ,PAMAM ,Immunoglobulin E ,Epitope ,Analytical Chemistry ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay [Medical Subject Headings] ,Epitopes ,Drug Discovery ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular [Medical Subject Headings] ,dendrimeric antigens ,Immunoassay ,Prueba de desgranulación de los Basófilos ,biology ,medicine.diagnostic_test ,Chemistry ,penicillin ,drug allergy ,basophil activation tests ,Penicilinas ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings] ,3. Good health ,Basophils ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,medicine.anatomical_structure ,Chemistry (miscellaneous) ,Molecular Medicine ,Hipersensibilidad a las drogas ,Cell activation ,Dendrimers ,Drug allergy ,Penicillins ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Structure-Activity Relationship [Medical Subject Headings] ,Article ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy [Medical Subject Headings] ,Drug Hypersensitivity ,lcsh:QD241-441 ,03 medical and health sciences ,Structure-Activity Relationship ,Antigen ,lcsh:Organic chemistry ,medicine ,Humans ,Physical and Theoretical Chemistry ,Organic Chemistry ,Allergens ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins [Medical Subject Headings] ,medicine.disease ,Basophil activation ,030104 developmental biology ,Immunology ,biology.protein ,Chemicals and Drugs::Biological Factors::Antigens::Allergens [Medical Subject Headings] ,Chemicals and Drugs::Macromolecular Substances::Polymers::Dendrimers [Medical Subject Headings] ,Anatomy::Cells::Myeloid Cells::Granulocytes::Basophils [Medical Subject Headings] - Abstract
Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy. Yes
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- 2018
33. Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America
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Patrizia Bonadonna, Kimberly G. Blumenthal, María José Torres, Eric Macy, Annick Barbaud, Pascal Demoly, David A. Khan, Miguel A. Park, Antonino Romano, Gülfem Çelik, Mariana Castells, Werner Aberer, Cristobalina Mayorga, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga [Spain], The Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Allergy Unit [Italy], Presidio Columbus [Italy]-Allergologia - Columbus - Policlinico Gemelli [Italy], Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Department of Chest Diseases [Ankara, Turkey], Division of Immunology and Allergy [Ankara, Turkey], Ankara University School of Medicine [Turkey]-Ankara University School of Medicine [Turkey], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Internal Medicine [Dallas, TX, USA], University of Texas Southwestern Medical Center [Dallas], Kaiser Permanente, Division of Allergic Diseases [Rochester, MN, USA], Mayo Clinic [Rochester], Division of Rheumatology, Allergy and Immunology [Boston, MA, USA] (Department of Medicine), Massachusetts General Hospital [Boston], Department of Dermatology [Graz, Austria], Medical University Graz, Division of Rheumatology, Immunology and Allergy [Boston, MSA, USA], Brigham and Women's Hospital [Boston], Service de dermatologie et allergologie [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Allergy Unit [Verona, Italy], Azienda ospedaliera universitaria integrata di Verona [Italy], [Torres,MJ, Mayorga,] Allergy Unit, National Network ARADyAL, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain. [Torres,MJ] BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain. [Romano,A] Allergy Unit, Presidio Columbus, Rome, Italy. IRCCS Oasi Maria S.S., Troina, Italy. [Celik,G] Department of Chest Diseases, Division of Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey. [Demoly,P] Hôpital Arnaud de Villeneuve, University Hospital of Montpellier and Sorbonne Universités, UPMC Paris , IPLESP, Equipe EPAR, Paris, France. [Khan,DA] Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA. [Macy,E] Kaiser Permanente Health Care Program, San Diego, CA, USA. [Park,M] Mayo Clinic College of Medicine, Division of Allergic Diseases, Mayo Clinic, Rochester, MN , USA. [Blumenthal,K] Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Aberer,W] Department of Dermatology, Medical University of Graz, Graz, Austria. [Castells,M] Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MSA, USA. [Barbaud,A] Sorbonne Universities, UPMC Univ Paris, Dermatology and Allergology Department, Tenon Hospital (AP-HP), Paris, France. [Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA (Pavilion C) Malaga, Spain. [Bonadonna,P] Allergy Unit, Azienda Ospedaliera Universitaria Intergrata of Verona, Verona, Italy., BMC, BMC, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
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0301 basic medicine ,Allergy ,[SDV]Life Sciences [q-bio] ,Provocation test ,Presumptive diagnosis ,Review ,Anafilaxia ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Health Care::Population Characteristics::Demography::Ethnic Groups [Medical Subject Headings] ,Clinical history ,Salud pública ,Diagnosis ,Immunology and Allergy ,media_common ,education.field_of_study ,Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings] ,Estados Unidos ,Health Care::Population Characteristics::Health::Public Health [Medical Subject Headings] ,3. Good health ,Humanos ,[SDV] Life Sciences [q-bio] ,Europe ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation [Medical Subject Headings] ,Pruebas cutáneas ,IgE ,Drug ,Hipersensibilidad a las drogas ,Europa ,Evaluación de Medicamentos ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,In vitro test ,media_common.quotation_subject ,Concordance ,Immunology ,Population ,Sensitization ,03 medical and health sciences ,Skin test ,medicine ,Hypersensitivity ,Intensive care medicine ,education ,business.industry ,Public health ,T-cells ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Anaphylaxis [Medical Subject Headings] ,medicine.disease ,United States ,Surgery ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests::Skin Tests [Medical Subject Headings] ,Grupos étnicos ,030104 developmental biology ,030228 respiratory system ,Drug provocation test ,Geographical Locations::Geographic Locations::Europe [Medical Subject Headings] ,business ,Unit States - Abstract
International audience; AbstractDrug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.
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- 2016
34. Development and Validation of a Model to Predict Severe Hospital-Acquired Acute Kidney Injury in Non-Critically Ill Patients
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Maria Luisa Martin, Silvia Pico, Elisard Huertas, Alfons Segarra, Joana Prat, Ricard Gavaldà, Maria Paz Marco, Maria J Torres, Jacqueline Del Carpio, Iñaki Romero, Mercedes Ibarz, Natalia Ramos, Gloria Falcon, Judith de la Torre, Marina Canales, Bruno Montoro, Nacho Nieto, Institut Català de la Salut, [Carpio JD] Department of Nephrology, Arnau de Vilanova University Hospital, 25198 Lleida, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institute of Biomedical Research (IRBLleida), 25198 Lleida, Spain. [Marco MP, Martin ML] Department of Nephrology, Arnau de Vilanova University Hospital, 25198 Lleida, Spain. Institute of Biomedical Research (IRBLleida), 25198 Lleida, Spain. [Ramos N] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [de la Torre J] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Department of Nephrology, Althaia Foundation, 08243 Manresa, Spain. [Prat J] Servei d’Informàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Department of Development, Parc Salut Hospital, 08019 Barcelona, Spain. [Torres MJ, Nieto N] Servei d’Informàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Department of Information, Southern Metropolitan Territorial Management, 08028 Barcelona, Spain. [Montoro B] Servei de Farmàcia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Segarra A] Department of Nephrology, Arnau de Vilanova University Hospital, 25198 Lleida, Spain. Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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medicine.medical_specialty ,enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::lesión renal aguda [ENFERMEDADES] ,Otros calificadores::/diagnóstico [Otros calificadores] ,Disease ,electronic health data records ,risk score ,Article ,Riscos per a la salut - Avaluació ,Internal medicine ,Ronyons - Malalties - Diagnòstic ,medicine ,Other subheadings::/diagnosis [Other subheadings] ,hospital-acquired ,Stage (cooking) ,Framingham Risk Score ,business.industry ,Incidence (epidemiology) ,Acute kidney injury ,Ronyons - Malalties - Prognosi ,General Medicine ,Odds ratio ,Stepwise regression ,medicine.disease ,Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury [DISEASES] ,técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::evaluación de riesgos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,acute kidney injury ,Medicine ,Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessment [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,business ,Kidney disease - Abstract
Lesión renal aguda; Registros electrónicos de datos de salud; Adquirido en el hospital Lesió renal aguda; Registres electrònics de dades de salut; Adquirit a l'Hospital Acute kidney injury; Electronic health data records; Hospital-acquired Background. The current models developed to predict hospital-acquired AKI (HA-AKI) in non-critically ill fail to identify the patients at risk of severe HA-AKI stage 3. Objective. To develop and externally validate a model to predict the individual probability of developing HA-AKI stage 3 through the integration of electronic health databases. Methods. Study set: 165,893 non-critically ill hospitalized patients. Using stepwise logistic regression analyses, including demography, chronic comorbidities, and exposure to risk factors prior to AKI detection, we developed a multivariate model to predict HA-AKI stage 3. This model was then externally validated in 43,569 non-critical patients admitted to the validation center. Results. The incidence of HA-AKI stage 3 in the study set was 0.6%. Among chronic comorbidities, the highest odds ratios were conferred by ischemic heart disease, ischemic cerebrovascular disease, chronic congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease and liver disease. Among acute complications, the highest odd ratios were associated with acute respiratory failure, major surgery and exposure to nephrotoxic drugs. The model showed an AUC of 0.906 (95% CI 0.904 to 0.908), a sensitivity of 89.1 (95% CI 87.0–91.0) and a specificity of 80.5 (95% CI 80.2–80.7) to predict HA-AKI stage 3, but tended to overestimate the risk at low-risk categories with an adequate goodness-of-fit for all risk categories (Chi2: 16.4, p: 0.034). In the validation set, incidence of HA-AKI stage 3 was 0.62%. The model showed an AUC of 0.861 (95% CI 0.859–0.863), a sensitivity of 83.0 (95% CI 80.5–85.3) and a specificity of 76.5 (95% CI 76.2–76.8) to predict HA-AKI stage 3 with an adequate goodness of fit for all risk categories (Chi2: 15.42, p: 0.052). Conclusions. Our study provides a model that can be used in clinical practice to obtain an accurate dynamic assessment of the individual risk of HA-AKI stage 3 along the hospital stay period in non-critically ill patients. This research received no external funding.
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- 2021
35. FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS
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Natalia Blanca-López, María José Torres, Carmen Martínez, J M García-Menaya, Jose A. Cornejo-Garcia, Gabriela Canto, Concepción Cordobés, Miguel Blanca, Gemma Amo, Elena García-Martín, Cristobalina Mayorga, Alfonso Ramos, José A. G. Agúndez, Gara Esguevillas, [Amo,G, Esguevillas,G, Martínez,C, Agúndez,JAG, García-Martín,E] Departamento de Farmacología, Universidad de Extremadura, Cáceres, Spain. [Cornejo,JA, Mayorga,C] Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [García-Menaya,JM, Cordobes,C] Servicio de Alergologia, Hospital Infanta Cristina, Badajoz, Spain. [Torres,MJ] UGC de Alergia, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Blanca-Lopez,N, Canto,G, Blanca,M] Servicio de Alergologia, Hospital Infanta Leonor, Madrid, Spain. [Ramos,A] Departamento de Matemáticas, Universidad de Extremadura, Cáceres, Spain., and This study was financed by grants PI12/00241, PI12/00324, PI15/00303, RETICS RD12/0013/0002, and RETICS RD16/0006/0004 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain, and GR15026 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union.
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0301 basic medicine ,Oxifenilbutazona ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Non-Narcotic::Anti-Inflammatory Agents, Non-Steroidal [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Benzoic Acids::Hydroxybenzoic Acids::Salicylic Acids::Aspirin [Medical Subject Headings] ,Fcε RI ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylpropionates::Ibuprofen [Medical Subject Headings] ,Naproxeno ,Pharmacology ,Immunoglobulin E ,Ibuprofeno ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyridines [Medical Subject Headings] ,Atopy ,chemistry.chemical_compound ,0302 clinical medicine ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylpropionates::Ketoprofen [Medical Subject Headings] ,Pharmacology (medical) ,Ácido flufenámico ,Cetoprofeno ,Sulfonas ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings] ,Original Research ,biology ,Acetaminofén ,Metamizole ,FCER1A ,Modelos logísticos ,Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazines::Piroxicam [Medical Subject Headings] ,Antiinflamatorios no Esteroideos ,Histamina ,Inmunoglobulina E ,Chemicals and Drugs::Organic Chemicals::Amides::Anilides::Acetanilides::Acetaminophen [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings] ,non-steroidal anti-inflammatory drugs (NSAIDS) ,MS4A2 ,Histamine ,medicine.drug ,Marcadores genéticos ,Chemicals and Drugs::Organic Chemicals::Sulfur Compounds [Medical Subject Headings] ,RI ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoles::Pyrazolones::Phenylbutazone::Oxyphenbutazone [Medical Subject Headings] ,Single-nucleotide polymorphism ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoles::Pyrazolones::Aminopyrine::Dipyrone [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Biological Markers::Genetic Markers [Medical Subject Headings] ,03 medical and health sciences ,Piroxicam ,Piridinas ,medicine ,Aspirina ,Dipirona ,Chemicals and Drugs::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Histamine [Medical Subject Headings] ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Indoles::Indomethacin [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Benzoic Acids::Aminobenzoic Acids::Anthranilic Acids::Fenamates::Flufenamic Acid [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthalenes::Naphthaleneacetic Acids::Naproxen [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,business.industry ,lcsh:RM1-950 ,biomarkers ,Fcε ,medicine.disease ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylacetates::Diclofenac [Medical Subject Headings] ,histamine ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030228 respiratory system ,chemistry ,Receptores de IgE ,Immunology ,biology.protein ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Fc::Receptors, IgE [Medical Subject Headings] ,hypersensitivity drug reactions ,Diclofenaco ,Polimorfismo de Nucleótido Simple ,business ,Etoricoxib ,Indometacina - Abstract
JOURNAL ARTICLE; The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity. From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA), propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone, or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837, and rs2251746; FCER1B rs1441586, rs569108, and rs512555; FCER1G rs11587213, rs2070901, and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742, and rs1049793 in the HDC, HNMT, and DAO genes. No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug, or clinical presentation) were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG) were strongly related (P < 0.001 and P = 0.005, respectively) with selective hypersensitivity to ibuprofen. With regard to patients with selective hypersensitivity to ASA, men were more prone to develop such a reaction than women (P = 0.011), and the detrimental DAO SNP rs10156191 in homozygosity increased the risk of developing such hypersensitivity (P = 0.039). Yes
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- 2016
36. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions
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Blanca-López N, Ja, Cornejo-García, Pérez-Alzate D, Pérez-Sánchez N, Mc, Plaza-Serón, Doña I, Mj, Torres, Canto G, Kidon M, James Richard Perkins, Blanca M, [Blanca-López,N, Pérez-Alzate,D, Canto,G] Allergy Service, Infanta Leonor Hospital, Madrid, Spain. [Cornejo-García,JA, Plaza-Serón,MC, Perkins,JR] Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. [Cornejo-García,JA, Pérez-Sánchez,N, Doña,I, Torres,MJ, Blanca, M] Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. [Kindon,M] Pediatric Allergy Clinic, Safra Children's Hospital, Chaim Sheba Medical Center, Tel Hashomer, Israel. Faculty of Pediatric Medicine, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel., and The present study was supported by grants from the Carlos III National Health Institute, Spanish Ministry of Economy and Competitiveness (grants cofunded by the European Regional Development Fund), RD12/0013/0001 (Red de Investigación de Reacciones Adversas a Alérgenos y Fármacos, RIRAAF Network), FIS PI12/02247, FIS PI13/02598, and the Andalusian Public Health Service (PI-0279-2012 and PI-0463-2013).
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Drug hypersensitivity reactions ,Adolescent ,NSAIDs ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Non-Narcotic::Anti-Inflammatory Agents, Non-Steroidal [Medical Subject Headings] ,Anti-Inflammatory Agents, Non-Steroidal ,Urticaria/angioedema o anafilaxia inducidas por un único AINE ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings] ,Diagnosis, Differential ,Drug Hypersensitivity ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnosis, Differential [Medical Subject Headings] ,Reacciones de hipersensibilidad a fármacos ,Risk Factors ,Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings] ,AINE ,Humans ,Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity [Medical Subject Headings] ,Single NSAID-induced delayed reactions ,Child ,Reacciones selectivas ,Reacciones tardías inducidas por un único AINE ,Single NSAID-induced urticaria/angioedema or anaphylaxis ,Named Groups::Persons::Age Groups::Child [Medical Subject Headings] - Abstract
Journal Article; Research Support, Non-U.S. Gov't; Review; Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. Yes A pesar de su eficacia en el tratamiento del dolor y la inflamación los antiinflamatorios no esteroideos (AINE), los medicamentos de mayor consumo mundial, también son la causa más frecuente de reacciones de hipersensibilidad a fármacos (RHFs) en cualquier tramo de edad. Aunque en muchas de estas reacciones se liberan mediadores inflamatorios en ausencia de reconocimiento inmunológico específico (intolerancia cruzada), un porcentaje considerable de las RHFs a AINE se producen a través de mecanismos inmunológicos (reacciones selectivas, SRs). En éstas participarían anticuerpos IgE específicos o células T. Las SRs son de gran interés en niños y adolescentes e incluyen un conjunto heterogéneo de entidades que comprenden desde manifestaciones clínicas de poca gravedad como la urticaria y el angioedema hasta otras como el síndrome de Stevens-Johnson y la necrolisis epidérmica tóxica, que pueden suponer una amenaza para la vida. En niños el paracetamol y el ibuprofeno son los medicamentos más frecuentemente implicados en las SRs mediadas por IgE aunque también se ha descrito la participación de las pirazolonas. Las reacciones mediadas por linfocitos T son menos frecuentes pero también se han descrito en relación con la administración de ibuprofeno, naproxeno y dipirona. En esta revisión analizaremos la literatura actual sobre las SRs en niños y adolescentes, centrándonos en los datos epidemiológicos, mecanismos y fármacos implicados, así como las pruebas disponibles para su diagnóstico.
- Published
- 2016
37. Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response
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Paloma Campo, Francisca Gómez, Maria Salas, Miguel Gonzalez, Francisca Palomares, Miguel Blanca, Enrique D. Gomez, Carmen Rondon, Cristobalina Mayorga, Tahia D. Fernandez, María José Torres, Inmaculada Doña, [Fernández,TD, Gómez,E, Gonzalez,M, Palomares,F, Mayorga,C] Research Laboratory-Allergy Unit, IBIMA-Regional University Hospital of Malaga, UMA, Malaga, Spain. [Doña,I, Campo,P, Rondon,C, Gomez,F, Salas,M, Blanca,M, Mayorga,C, Torres,MJ] Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Malaga, Spain., and 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 -ERDF
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Male ,Rinitis alérgica ,medicine.medical_treatment ,Dermatophagoides pteronyssinus ,Plasma cell ,Immunoglobulin E ,medicine.disease_cause ,Anatomy::Hemic and Immune Systems::Immune System::Antibody-Producing Cells::B-Lymphocytes [Medical Subject Headings] ,Immunoglobulin G ,Immune tolerance ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Allergen ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunosuppression::Desensitization, Immunologic [Medical Subject Headings] ,Alérgenos ,Desensitization (medicine) ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes [Medical Subject Headings] ,Multidisciplinary ,biology ,Cell Differentiation ,Linfocitos T ,Prognosis ,Diseases::Respiratory Tract Diseases::Nose Diseases::Rhinitis [Medical Subject Headings] ,medicine.anatomical_structure ,Treatment Outcome ,Anatomy::Cells::Antibody-Producing Cells::B-Lymphocytes::Plasma Cells [Medical Subject Headings] ,Inmunoglobulina G ,Female ,Linfocitos B ,Adult ,Plasma Cells ,B-Lymphocyte Subsets ,Células plasmáticas ,Article ,medicine ,Immune Tolerance ,Animals ,Humans ,Cell Lineage ,Lymphocyte Count ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G [Medical Subject Headings] ,business.industry ,Case-control study ,Immunotherapy ,Allergens ,Desensibilización inmunológica ,Rhinitis, Allergic ,Desensitization, Immunologic ,Case-Control Studies ,Immunology ,biology.protein ,Chemicals and Drugs::Biological Factors::Antigens::Allergens [Medical Subject Headings] ,business ,Immunologic Memory ,Biomarkers - Abstract
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. Yes
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- 2015
38. Hypersensitivity reactions to β-lactams: relevance of hapten-protein conjugates
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Ariza A, CRISTOBALINA MAYORGA, Td, Fernandez, Barbero N, Martín-Serrano A, Pérez-Sala D, Fj, Sánchez-Gómez, Blanca M, Mj, Torres, Mi, Montanez, [Ariza,A, Mayorga,C, Fernández,TD, Martín-Serrano,A, Montañez,MI] Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. [Mayorga,C, Blanca,M, Torres,MJ] Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Málaga, Spain. [Barbero,N, Montañez,MI] BIONAND—Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain. [Barbero,N] Department of Organic Chemistry, Faculty of Sciences, IBIMA, University of Malaga, Malaga, Spain. [Pérez-Sala,D, Sánchez-Gómez,FJ] Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain., and The study was funded by FIS-Thematic Networks and Cooperative Research Centres (RIRAAF/RD012/0013), Junta de Andalucía (CTS 06603, PI-0545-2010, and PI-0699-2011), ISCIII (PI12/02529), Fundación Salud 2000, MINECO (SAF2012-36519 to DPS), and the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 300230.
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Betalactams ,Proteins ,Blood Proteins ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins [Medical Subject Headings] ,Immunologic Tests ,Portador ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes::Haptens [Medical Subject Headings] ,beta-Lactams ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests [Medical Subject Headings] ,Anti-Bacterial Agents ,Drug Hypersensitivity ,Hapten ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Proteínas ,Betalactamas ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams [Medical Subject Headings] ,Humans ,Hapteno ,Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity [Medical Subject Headings] ,Carrier ,IgE ,Carrier Proteins ,Haptens ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings] - Abstract
Journal Article; Research Support, Non-U.S. Gov't; Review; β-Lactams (BL) are the drugs most frequently involved in allergic reactions. They are classified according to their chemical structure as penicillins, cephalosporins, monobactams, carbapenems, and clavams. All BL antibiotics have a BL ring that is fused to a 5-member or 6-member ring (except in monobactams) and has 1, 2 or 3 side chains (except in clavams). Differences in chemical structure mean that a wide range of BLs are recognized by the immune system, and patients may experience clinical reactions to one BL while tolerating others. Diagnosis is based on skin and in vitro testing, although both display low sensitivity, possibly because they are based on drugs or drug conjugates that are not optimally recognized by the immune system. BLs are haptens that need to bind to proteins covalently to elicit an immune response. These drugs have a high capacity to form covalent adducts with proteins through nucleophilic attack of amino groups in proteins on the BL ring. Allergenic determinants have been described for all BLs, although benzylpenicillin is the most widely studied. Moreover, formation of BL-protein adducts is selective, as we recently demonstrated for amoxicillin, which mainly modifies albumin, transferrin, and immunoglobulin heavy and light chains in human serum. Given the complexity of BL allergy, understanding the immunological mechanisms involved and optimization of diagnostic methods require multidisciplinary approaches that take into account the chemical structures of the drugs and the carrier molecules, as well as the patient immune response. Yes Las betalactamas (BL) son los fármacos implicados más frecuentemente en reacciones alérgicas. Se clasifican según su estructura química en penicilinas, cefalosporinas, monobactamas, carbapenems y clavamas. Poseen un anillo betalactámico que, excepto en las monobactamas, está fusionado a un anillo de cinco o seis miembros y, excluyendo las clavamas, tienen 1, 2 o 3 cadenas laterales. Las diferencias en las estructuras químicas resultan en un amplio rango de BLs, que puede ser discriminado por el sistema inmune, con inducción de reacciones clínicas a una BL y tolerancia a otras. El diagnóstico está basado en pruebas cutáneas e in vitro, aunque ambas presentan una baja sensibilidad. Esto podría deberse a que los fármacos o conjugados de fármacos empleados en estos tests que no se reconocen de manera óptima por el sistema inmune. Las BLs son haptenos que necesitan de su unión covalente a proteínas para inducir una respuesta inmunológica. Estos fármacos presentan una elevada capacidad para formar aductos covalentes con proteínas mediante el ataque nucleofílico de grupos aminos de proteínas al anillo BL. Aunque la bencilpenicilina ha sido la mejor estudiada, también se han descrito determinantes alergénicos del resto de BLs. Además, la formación de los aductos BLs-proteína muestra selectividad, así se ha demostrado recientemente para la amoxicilina, que principalmente modifica la albúmina en suero (HSA), la transferrina y las cadenas ligeras y pesadas en suero humano. Dada la complejidad de la alergia a BL, el conocimiento de los mecanismos inmunológicos implicados y la optimización de los métodos diagnósticos requieren de abordajes multidisciplinares teniendo en cuenta tanto la estructura química de los fármacos y de las moléculas portadoras, como las respuestas de los pacientes.
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- 2015
39. Four years into the COVID-19 pandemic: Timely published articles for patient care and EAACI's leadership role.
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Torres MJ, Klimek L, Agache I, Jutel M, Akdis M, Shamji MH, and Akdis CA
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- 2024
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40. Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.
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Pfaar O, Sousa-Pinto B, Papadopoulos NG, Larenas-Linnemann DE, Ordak M, Torres MJ, Mösges R, Klimek L, Zuberbier T, Matricardi PM, Berger UE, Berger M, Dramburg S, Mahler V, Toppila-Salmi SK, Bergmann KC, Ollert M, Tripodi S, Jutel M, Agache I, Eguiluz-Gracia I, Canonica GW, Akdis CA, Sokolowska M, Sofiev M, Shamji MH, Czarlewski W, Fonseca JA, Bedbrook A, and Bousquet J
- Abstract
In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2024
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41. Impact of breastfeeding on ICU admissions and need for mechanical ventilation in infants younger than 6 months with RSV+ bronchiolitis. An observational study.
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Jiménez-Nogueira E, Bueno-Rebollo C, García-Jerez B, Callejón-Fernández E, Díaz-Torres MJ, González-Jiménez Y, Lozano-Paniagua D, Juárez-Marruecos P, Nievas-Soriano BJ, and Bonillo-Perales A
- Abstract
Introduction: This work aimed to analyze whether breastfeeding is a predictive factor for admission to ICU or needing mechanical ventilation in children under 6 months with RSV+ respiratory infection., Methods: A retrospective cohort study was performed in three hospitals. Binary and multiple logistic regression analyses were performed to evaluate the association of variables with admission to the ICU or receiving mechanical ventilation., Results: We analyzed 414 admissions, of which 293 (70.8%) had received breastfeeding, 43 (8.1%) were admitted to the ICU, and 26 (5.4%) required mechanical ventilation. Bivariate analysis showed that breastfeeding for at least 15 days and a longer duration of breastfeeding were associated with a lower risk of admission to the ICU and requiring mechanical ventilation. Multivariate analysis showed that not having been breastfed for at least 1 month was predictive of ICU admission; not having been breastfed for at least 2 months was predictive of needing mechanical ventilation., Conclusions: Breastfeeding for as little as 15-28 days could be associated with a lower risk of ICU admission and requiring mechanical ventilation in infants younger than 6 months admitted for RSV+ bronchiolitis. Since breastfeeding is one of the few protective factors that can be promoted, this finding is relevant for current clinical practice and the development of health promotion programs. Future studies can compare their results to ours., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)
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- 2024
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42. Working with companies that manufacture breastmilk substitutes: An EAACI position paper.
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Arasi S, Caubet JC, Ceylan O, Eguíluz-Gracia I, Del Giacco S, Gelincik A, Jutel M, Meyer R, Ollert M, and Torres MJ
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- Humans, Infant, Infant, Newborn, Infant Formula economics, Milk Substitutes, Europe, Female, Breast Feeding, Food Industry, Infant Nutritional Physiological Phenomena, Milk, Human immunology
- Abstract
Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2024
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43. Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams.
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Fernandez-Santamaria R, Ariza A, Bogas G, Salas M, Calvo-Serrano S, Frecha C, Mayorga C, Torres MJ, and Fernandez TD
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- Humans, Receptors, CCR7 metabolism, Cytokines metabolism, Amoxicillin metabolism, Clavulanic Acid metabolism, CD40 Antigens, Dendritic Cells metabolism, Hypersensitivity, Immediate, Hypersensitivity metabolism
- Abstract
Background: Amoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs)., Methods: mDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3
+ , CD4+ , CD8+ , CD4+ Th1, and CD4+ Th2, by flow cytometry., Results: Higher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+ Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV., Conclusions: mDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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44. LPS in combination with amoxicillin increases BAT sensitivity to amoxicillin IgE-mediated hypersensitivity.
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Céspedes JA, Fernández-Santamaría R, Bogas G, Veguillas AA, Doña I, Salas M, Labella M, Fernández Duarte TD, Mayorga C, Torres MJ, and Frecha CA
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- 2024
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45. Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis.
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Palomares F, Pérez-Sánchez N, Nieto N, Núñez R, Cañas JA, Martín-Astorga MDC, Cruz-Amaya A, Torres MJ, Eguíluz-Gracia I, Mayorga C, and Gómez F
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- Humans, Female, Male, Adult, Cytokines metabolism, Lymphocytes immunology, Lymphocytes metabolism, Plant Proteins immunology, Lymphocyte Activation immunology, Young Adult, Middle Aged, Food Hypersensitivity immunology, Immunity, Innate, Antigens, Plant immunology, Carrier Proteins immunology
- Abstract
Background: Immunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization., Methods: The immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy., Results: Our results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3
+ Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+ Th1- and FOXP3+ Treg cell differentiation., Conclusions: The results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo , as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets., 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 © 2024 Palomares, Pérez-Sánchez, Nieto, Núñez, Cañas, Martín-Astorga, Cruz-Amaya, Torres, Eguíluz-Gracia, Mayorga and Gómez.)- Published
- 2024
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46. Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses.
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Pérez-Moreno AM, Aranda CJ, Torres MJ, Mayorga C, and Paris JL
- Abstract
Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N
2 adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses., (© 2024. The Author(s).)- Published
- 2024
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47. Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.
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Indo S, Orellana-Serradell O, Torres MJ, Castellón EA, and Contreras HR
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- Male, Humans, Androgen Antagonists, Transcription Factors, Cell Line, Tumor, Receptors, Androgen metabolism, Epithelial-Mesenchymal Transition genetics, Prostatic Neoplasms metabolism, Prostatic Neoplasms, Castration-Resistant pathology, Benzamides, Nitriles, Phenylthiohydantoin
- Abstract
The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial-mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated. EMT genes, Twist and Zeb1, and the androgen receptor (AR) were evaluated through an RT-qPCR and Western blot in nuclear and cytosolic fractions of REST-overexpressing 22rv1 cells (22rv1-REST). The migratory and invasive capacities of 22rv1-REST cells were evaluated via Transwell
® assays with and without Matrigel, respectively, and their viability for enzalutamide via MTT assays. The 22rv1-REST cells showed decreased nuclear levels of Twist, Zeb1, and AR, and a decreased migration and invasion and a lower viability for ENZ compared to the control. Results were expressed as the mean + SD of three independent experiments (Mann-Whitney U test, Kruskal-Wallis, Tukey test). REST behaves like a tumor suppressor, decreasing the aggressiveness of 22rv1 cells, probably through the repression of EMT and the neuroendocrine phenotype. Furthermore, REST could represent a response marker to ENZ in PCa patients.- Published
- 2024
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48. Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.
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Eguiluz-Gracia I, Parkin RV, Layhadi JA, Palmer E, Meng X, Zhu R, Sahiner U, Durham SR, Torres MJ, Mayorga C, Rondon C, and Shamji MH
- Abstract
Background: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients., Methods: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG
4 , IgA1 and IgA2 ) and their inhibitory capacity were measured at multiple timepoints., Results: The allergen concentration tolerated increased significantly at 6 months (Group A; p = .047) and 24 months (Group B; p = .049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71-fold, p = .027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p = .047 and p = .0039) and sIgA2 to Phl p in Group B (p = .032 and p = .0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen-IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra-nasally in Group A (serum; 𝜌 = -.47, p = .0006, nasal; 𝜌 = -.38, p = .0294)., Conclusions: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)- Published
- 2024
- Full Text
- View/download PDF
49. Drug hypersensitivity: Past, present and future.
- Author
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Torres MJ and Doña I
- Subjects
- Humans, Basophils, Basophil Degranulation Test, Drug Hypersensitivity diagnosis, Drug Hypersensitivity etiology, Hypersensitivity, Immediate
- Published
- 2024
- Full Text
- View/download PDF
50. 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
- Full Text
- View/download PDF
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