Pharmacogenomics of Drug Hypersensitivity

Kuruvilla, Rebecca; Scott, Kathryn A.; Pirmohamed, Munir

doi:10.1016/j.iac.2022.01.006

Cited by 8 publications

(9 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic testing has a potential role among strategies used for prevention in identifying whether an individual may be susceptible to developing a serious adverse reaction from a particular drug, as pharmacogenomic studies have revealed strong associations between SCARs and genes encoding HLA molecules in a drug and ethnicity-specific pattern ( Su et al, 2016 ; Phillips, 2018 ; Kuruvilla et al, 2022 ). Thus, pharmacogenetic testing in SCARs has been proposed for prevention, monitoring, and diagnosis ( Pirmohamed, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacogenetic studies have identified some HLA-I alleles as genetic risk factors for well-characterized type IV hypersensitivity reactions in relationship with certain drugs such as abacavir, carbamazepine, and allopurinol in selected populations, and genetic tests are being implemented to avoid their use and prevent severe reactions in patients at risk ( Su et al, 2016 ; Kuruvilla et al, 2022 ; Wang et al, 2022 ); HLA-B*57:01 testing has been conducted prior to prescription in HIV patients (the prototypical case) due to its 100% negative predictive value (NPV) and 55% positive predictive value (PPV) to predict abacavir hypersensitivity ( Phillips and Mallal, 2009 ). Nonetheless, there are no specific biomarkers available for most of the drugs inducing SCARs, and active research is being conducted to identify suitable biomarkers for common inducers of severe reactions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study

Bellón

Lerma²,

Guijarro³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher’s exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364–130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28–252.6; p = 4.0 × 10−3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study

Bellón

Lerma²,

Guijarro³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

Section: Clinical Application and Challenges Of Omic‐based Studiesmentioning

confidence: 99%

“…Initial omics studies have mainly relied on GWAS, which, despite their limitations, have shown to be a useful tool in pharmacogenomics. For example, in some populations they have led to specific recommendations before the administration of several drug types to prevent severe allergic reactions, 165 and some polymorphisms have been also associated with the response to inhaled corticosteroids 166,167 and to long-acting β2 adrenoceptor agonists in asthmatics. [168][169][170] Nowadays, data from high-throughput omics technologies are substantially improving our knowledge on the mechanisms underlying allergic diseases, which should ideally shunt diagnosis and treatment from a clinical phenotype-based approach towards a clinical endotype-based strategy.…”

Section: Clini C Al Appli C Ati On and Challeng E S Of Omi C-ba S Ed ...mentioning

confidence: 99%

Omics technologies in allergy and asthma research: An EAACI position paper

Radzikowska

Baerenfaller

Cornejo-García

et al. 2022

Allergy

View full text Add to dashboard Cite

Allergic diseases and asthma are heterogenous chronic inflammatory conditions with several distinct complex endotypes. Both environmental and genetic factors can influence the development and progression of allergy. Complex pathogenetic pathways observed in allergic disorders present a challenge in patient management and successful targeted treatment strategies. The increasing availability of high-throughput omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics allows studying biochemical systems and pathophysiological processes underlying allergic responses. Additionally, omics techniques present clinical These different cellular components are tightly interconnected with TA B L E 1 Summary of methods, protocols, and data analysis pipelines most frequently used in omics approaches for allergic diseases research Methods and protocols Data analysis pipeline Mechanisms of allergic diseases Genomics and transcriptomics Microarray 181,182GWAS 183 and RNA microarray bioinformatics 184,185

show abstract

“…Lower PPV means that fewer patients with a positive test are likely to develop a reaction and more people need to be tested to prevent one. This is not fully understood but may be related to the presence of concomitant disease states or other genetic factors, for example, renal impairment in the context of allopurinol treatment, and CYP2C9 metaboliser status in the context of phenytoin treatment 4 . Of note, hypersensitivity reactions can be dose‐dependent but do not exhibit a typical dose–response relationship 4 .…”

mentioning

confidence: 99%