Differential cytokine and transcription factor expression in patients with allergic reactions to drugs

Cornejo-García, J.A.; Fernandez, Tahía D.; Torres, Marı́a José; Carballo, Miguel; Hernán, Imma; Antúnez, C.; Blanca, Miguel; Mayorga, Cristobalina

doi:10.1111/j.1398-9995.2007.01542.x

Cited by 47 publications

(37 citation statements)

References 33 publications

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“…More specifically, the IgE response shows a Th2 pattern with an increase of IL-4 and IL-13 and a downregulation of IFN-γ and IL-12 [62,63]. Involvement of TNF-α in anaphylactic reactions has also been reported [62].…”

Section: Monitoring the Acute Phasementioning

confidence: 93%

Drug-Induced Anaphylaxis

Blanca‐López

Plaza-Serón

Cornejo-García

et al. 2015

Curr Treat Options Allergy

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Section: Monitoring the Acute Phasementioning

confidence: 93%

Drug-Induced Anaphylaxis

Blanca‐López

Plaza-Serón

Cornejo-García

et al. 2015

Curr Treat Options Allergy

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“…Monitoring the acute phase of DHRs through analysis of activation status and cell populations using flow cytometry techniques, immunohistochemistry, and transcriptomic assays of gene expression has proven to be a useful approach for better classifying and understanding these reactions [128][129][130][131][132].…”

Section: Further Approaches For Deciphering Dhrsmentioning

confidence: 99%

The Genetics of Drug Hypersensitivity Reactions

Cornejo-García

Jurado‐Escobar

Doña

et al. 2016

J Investig Allergol Clin Immunol

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Drug hypersensitivity reactions (DHRs) are a major problem for healthcare systems, regulatory agencies, and the pharmaceutical industry. DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice. Key words: Drug hypersensitivity. Immediate and nonimmediate reactions. Cross-intolerance. Single-nucleotide polymorphisms. Genome-wide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son un problema preocupante para los sistemas de salud, las agencias reguladoras y la industria. Además de la diversidad de mecanismos implicados, las RHFs incluyen un conjunto heterogéneo de entidades clínicas que pueden amenazar la vida del paciente. A esta complejidad se añade el hecho de que, además de factores ambientales, en ellas participan factores individuales. A pesar del considerable esfuerzo desarrollado en los últimos años en la identificación de los factores individuales que predisponen a la aparición de estas reacciones, nuestro conocimiento sobre la base genética de las RHFs es todavía limitado. En esta revisión se presentan los datos disponibles sobre la genética de las RHFs, tomando como modelo las reacciones mediadas por mecanismos inmunológicos específicos (anticuerpos IgE y células T, reacciones inmediatas y no inmediatas) así como las mediadas por mecanismos farmacológicos (intolerancia cruzada a anti-inflamatorios no esteroideos). También se destacan las aproximaciones tecnológicas que pueden proporcionar información fundamental sobre los mecanismos moleculares que subyacen en estas reacciones. Creemos que este manuscrito será útil no solo para alergólogos e investigadores básicos en éste área, sino también para otros profesionales de la medicina que pueden encontrarse con este tipo de reacciones en su práctica clínica. Palabras clave: Hipersensibilidad a fármacos. Reacciones inmediatas y no inmediatas. Intolerancia cruzada. Polimorfismos de un único nucleótido. Estudios de asociación de genoma completo.

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“…Barhl1, CCNT2 and Hmx-2 have not previously been associated with NIUA or allergic diseases; however, GATA is a superfamily of transcription factors implicated in the regulation of cellular differentiation of important immune cells, such as basophils [43] and eosinophils [44]. Specifically, GATA-3 is implicated in the development of Th2 responses in allergic dermatitis [45,46] and in selective, single NSAID-induced urticaria/angioedema [47]. Furthermore, it has been suggested that GATA-3 blockage by corticosteroids could be used as a treatment for allergies due to the inhibition of the Th2 response [48].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema

Plaza-Serón

Blanca‐López²,

Pérez‐Sánchez³

et al. 2016

Int Arch Allergy Immunol

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Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent agents involved in hypersensitivity drug reactions, with NSAID-induced urticaria and/or angioedema (NIUA) being the most common entity. Mast cells are key players in NIUA and are activated by thymic stromal lymphopoietin (TSLP). This cytokine functions through recognition by its receptor, composed of IL7Rα (interleukin-7 receptor alpha) and TSLPR (TSLP receptor). These genes have been previously associated with other inflammatory diseases. Methods: We assessed the genetic association between single nucleotide polymorphisms (SNPs) in TSLP, IL7R and TSLPR and NIUA in Spanish individuals, using genotyped and imputed data. A total of 369 unrelated NIUA patients and 580 NSAID-tolerant control subjects were included, and 6 SNPs in TSLP, 6 in IL7R and 3 in TSLPR were genotyped. Further variants were imputed using Mach and the 1,000 Genomes Project (Phase 3) data. Association testing and statistical analyses were performed with Mach2dat and R. Results: A total of 139 SNPs were tested for association following quality control. Two SNPs in TSLP (rs1816678 and rs764917) showed a nominal association (p = 0.033 and 0.024, respectively) with NIUA, although these results were not statistically significant after correcting for multiple comparisons. Conclusions: Although TSLP, IL7R and TSLPR are important genes involved in the development of the inflammatory response, we found no significant genetic association with NIUA in our population for common SNPs in these genes.

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Differential cytokine and transcription factor expression in patients with allergic reactions to drugs

Cited by 47 publications

References 33 publications

Drug-Induced Anaphylaxis

Drug-Induced Anaphylaxis

The Genetics of Drug Hypersensitivity Reactions

Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema

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