Estudio farmacogenético de reacciones de hipersensibilidad a antibióticos bet-lactámicos y a antiinflamatorios no esteroideos

[ES] Estudio farmacogenético de 22 polimorfismos en 13 genes de citocinas en 443 individuos con reacciones de hipersensibilidad a los antibióticos beta-lactámicos (BL) y a los antiinflamarios no esteroideos (AINE). En este trabajo se han esteblecido 3 grupos de análisis: pacientes con hipersensibilidad a los BL vs sus controles, pacientes con hipersensibilidad a los AINE vs sus controles y un grupo comparativo con ambos tipos de pacientes, ya que se trata de dos patologías muy diferentes, en el caso de los BL mediada por un mecanismo inmunológico y en el caso de los AINE mediada por un mecanismo no inmunológico. En el grupo de pacientes con hipersensibilidad a los BL, se han incluido 202 individuos: 104 controles estudiados por reacción adversa a un BL y resultado negativo en el estudio y tolerancia comprobada a estos antibióticos mediante la prueba de exposición, 27 de los cuáles eran atópicos y 98 pacientes con reacciones alérgicas inmediatas a los BL diagnosticados mediante el protocolo diagnóstico de alergia a los BL (criterios ENDA). Se ha encontrado asociación con algunos polimorfismos de la agrupación de la IL-1, IFNG, IL4 e IL4RA y la variable clínica atopia dentro del grupo de pacientes con reacciones inmediatas a los BL, estableciendo la posible influencia de la atopia en las reacciones inmediatas a este tipo de antibióticos y coincidiendo estos resultados con diversos estudios en la bibliografía. En el grupo de pacientes con hipersensibilidad a los AINE, se han incluido 241 individuos: 156 controles sin antecedentes y síntomas de asma, poliposis nasosinusal, AINE, alergia y atopia y 85 pacientes diagnosticados de enfermedad respiratoria exacerbada por los AINE (EREA) según el protocolo diagnóstico de reacciones de hipersensibilidad a los AINE. Se han encontrado fuertes asociaciones con polimorfismos en los genes TNFA, IL4 e IL10 y la hipersensibilidad a los AINE, por lo que estos tres genes podrían considerarse genes candidato en su asociación con la hipersensibilidad a los AINE y es que polimorfismos en estos tres genes podrían incrementar el riesgo al desarrollo de la EREA, apoyando nuestros resultados en base a numerosos estudios en la bibliografía. En el grupo en el que se establece un análisis comparativo entre los 98 pacientes con reacciones alérgicas inmediatas a los BL y los 85 pacientes con reacciones de hipersensibilidad a los AINE, se encuentra asociación de nuevo con polimorfismos en los genes TNFA, IL4 e IL10, confirmando que el peso de las asociaciones recae en la EREA y no en las reacciones inmediatas a los BL que se comportan en este caso como controles

Atopy Can Be an Interfering Factor in Genetic Association Studies of ß-Lactam Allergy

[EN] Genetic and environmental factors are involved in immediate hypersensitivity reactions to ß-lactam antibiotics. Several genes have been associated with immediate hypersensitivity reactions to ß-lactams, including those encoding cytokines and receptors involved in the synthesis of IgE (FCER1), as well as signal transduction proteins and products released by mast cells. Nevertheless, analysis of publications reporting on genetic association studies in patients allergic to ß-lactams reveals that most were performed in 3 main populations and, in most cases, by the same groups of investigators, who progressively increased the population sample in successive studies. Most of the publications reported a series of concerns, namely, the diagnosis was not always based on skin or challenge tests, tolerance to ß-lactams in controls was not proved, and atopy was not taken into account

Polymorphisms in Human IL4, IL10, and TNF Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease

[EN]Background: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. Methods: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. Results: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. Conclusions: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.Sociedad Española de Alergología e Inmunología Clínica; Fundación de Investigación Médica Caja de Burgos; Instituto de Salud Carlos III’s Thematic Network of Cooperative Research in Health-RETICS (Thematic network of research in health Asthma, Adverse and Allergic Reactions, ARADYAL)

Polymorphisms in Human <i>IL4</i>, <i>IL10</i>, and <i>TNF</i> Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease

Background: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. Methods: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. Results: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. Conclusions: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD