Polymorphism of <i>IL10, IL4, CTLA4</i>, and <i>DAO</i> Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Vasconcelos, Luciana Mabel Ferreira; Rodrigues, Rodrigo Rodrigues; Albuquerque, Andressa Almeida; Barroso, Gabrielle Dantheias; Sasahara, Greyce Luri; Ferreira, Janaíra Fernandes Severo; Francelino, Eudiana Vale; Cardoso, Cynthia Chester; Rabenhorst, Sílvia Helena Barem; Almeida, Thereza Lúcia Prata de; Nagão-Dias, Aparecida Tiemi

doi:10.1002/jcph.986

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…However, in a previous study we did not find associations between NSAID-induced hypersensitivity and common SNPs for 3 histamine receptors [110], although we did find that the diamine oxidase (histaminase) missense polymorphism rs10156191 (Thr16Met), which affects histamine metabolism, was associated with NIUA and NERD [111]. The histaminase 8956 C>G variant was shown to be associated with NIUA in a Brazilian population [112]. We recently found associations between NIUA and several polymorphisms in genes involved in mast cell activation: rs12746200 (PLA2G4A), rs2228246 (PLCG1), and rs1805034 (TNFRS11A) [113].…”

Section: Other Variants Outside Eicosanoid Biosynthesiscontrasting

confidence: 68%

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Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

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Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to β-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists. Key words: Drug hypersensitivity. Immunologically-mediated reactions. Cross-hypersensitivity. Single-nucleotide polymorphisms. Genomewide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son respuestas no predecibles que se producen en algunos sujetos y que representan un serio problema de salud pública debido al número de pacientes implicados y a su potencial gravedad. Además de factores ambientales, en estas reacciones también participan factores genéticos, cuya influencia está, en la mayoría de los casos, aún por dilucidar. En este manuscrito describiremos la información disponible sobre la base genética de los tipos más frecuentes de RHFs, tanto de las mediadas inmunológicamente como de aquellas en las que no se requiere reconocimiento antigénico. En el primer grupo nos ocuparemos de las reacciones inmediatas a antibióticos β-lactámicos, que han sido asociadas con variantes relacionadas con la IgE (IL13, IL4R, LGALS3 y NOD2) y la presentación antigénica (HLA-DRA), y de las reacciones no inmediatas a diferentes grupos de medicamentos (alopurinol, anticonvulsivos, antibióticos y antiretrovirales), relacionadas fundamentalmente con polimorfismos en el sistema HLA. En el segundo grupo nos centraremos en las reacciones inducidas por antiinflamatorios no esteroideos (AINE), que han sido asociadas básicamente con variantes en enzimas y receptores de la vía del ácido araquidónico (ALOX5, ALOX5AP, PTGDR y CYSLTR1, entre otros). Esta revisión puede ser de interés no sólo para alergólogos, sino para los profesionales de otras ...

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Section: Other Variants Outside Eicosanoid Biosynthesiscontrasting

confidence: 68%

“…Finally, further associations have been found with the adenosine receptor A3 gene (-1050G>T and -564C>T) [117], IL4 (-589T>C) [112,118], IL10 (-1082 G>A) [112], CTLA (49A>G) [112], nitric oxide synthase 2 [119], and the HLA system [120][121][122].…”

Section: Other Variants Outside Eicosanoid Biosynthesismentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

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“…The immune checkpoint inhibitor again seems to alter the co‐stimulatory/co‐inhibitory balance, permitting the development of dacarbazine‐induced liver injury in almost all treated patients. Finally, it has been reported that polymorphisms in regulatory targets of immune responses such as CTLA‐4 and IL‐10 could modulate susceptibility to nonsteroidal anti‐inflammatory drug and efavirenz hypersensitivity reactions. Collectively, these data indicate that immune checkpoints act to regulate the strength of the drug‐specific T‐cell response and hence impact on the balance between tolerance and hypersensitivity (Figure ).…”

Section: Immune Checkpointsmentioning

confidence: 99%

Immune dysregulation increases the incidence of delayed‐type drug hypersensitivity reactions

Naisbitt

Olsson‐Brown

Gibson

et al. 2019

Allergy

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Delayed-type, T cell-mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug-peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity. K E Y W O R D Sdrug hypersensitivity, HLA, immune checkpoint inhibitors, regulation, T cells

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“…142 Furthermore, T cells and also B lymphocytes are involved in BL-induced NIR, as demonstrated by IgG secretion and increased CD27 expression in response to soluble piperacillin. 143 Different gene polymorphisms have been associated with hypersensitivity to NSAIDs: two intronic variants in centrosomal protein of 68 kDa with single-NSAID-induced urticaria/angioedema or anaphylaxis144 ; IL10 polymorphism with chemically unrelated NSAIDs hypersensitivity; and specific polymorphisms in CTLA4 or diamine oxidase genes although with a protective effect 145.…”

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confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Allergy

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Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369

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Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Cited by 13 publications

References 34 publications

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Immune dysregulation increases the incidence of delayed‐type drug hypersensitivity reactions

Recent developments and highlights in drug hypersensitivity

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