Significant HLA class I type associations with aromatic antiepileptic drug (AED)-induced SJS/TEN are different from those found for the same AED-induced DRESS in the Spanish population

Ramírez, Elena; Bellón, Teresa; Tong, Hoi Y.; Borobia, Alberto M.; Abajo, Francisco J. de; Lerma, Victoria; Hidalgo, Miguel A. Moreno; Castañer, J.; Cabañas, Rosario; Fiandor, Ana; González-Ramos, J.; Pinto, Pedro Herranz; Cachafeiro, Lucía; González‐Herrada, Carlos; González, Olga Martínez; Aramburu, J. A.; Laosa, Olga; Hernández, Rafael; Carcas, Antonio J.; Frías, Jesús

doi:10.1016/j.phrs.2016.11.027

Cited by 64 publications

(41 citation statements)

References 45 publications

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“…This seminal study showed that the HLA‐B*15:02 allele was present in 100% of SJS/TEN cases, but in only 3% of carbamazepine‐tolerant controls and 8.6% of drug naïve controls, equating to 97% specificity and 100% sensitivity (Table ). Over the past decade, numerous studies have corroborated this association not only in Han Chinese populations, but also in Thai, Indian, Vietnamese, Malaysian, Spanish Romani, Javanese/Sudanese and other populations (Table ). Conversely, investigations of HLA‐B*15:02 ‐restricted carbamazepine‐induced SJS/TEN in European and Japanese studies failed to find a significant association (Table ), which is not surprising given the relatively low frequency of this HLA allele in these populations (Table ).…”

Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

“…The second GWAS study by McCormack et al also demonstrated increased risk of carbamazepine‐induced MPE, DRESS and SJS/TEN in Europeans (Table ). Corroborating these GWAS investigations, reports from Han Chinese (Taiwan), European, Canadian (mixed ethnicity), Spanish Romani and Korean confirmed a strong HLA‐A*31:01 association with carbamazepine‐induced DRESS and/or MPE, but not for SJS/TEN (Table ).…”

Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

“…Whilst there has been a case study purporting the presence of HLA‐A*31:01‐ restricted carbamazepine‐specific T‐cells in a patient with MPE, there are limited studies addressing the broader HLA‐A19 serotypes (includes A29, A30, A31, A32, A33, A74; selected alleles shown in Figure ) and AED‐induced cADRs. More recently, in a study by Ramirez et al three of four carbamazepine‐induced DRESS cases expressed a HLA‐A19 serotype ( HLA‐A*31:01 , ‐A*32:01 and ‐A*33:03 ). Associations have also been identified between HLA‐A*33:03 and carbamazepine‐induced DRESS, as well as for carbamazepine‐induced SJS/TEN .…”

Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

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HLA‐associated antiepileptic drug‐induced cutaneous adverse reactions

Mullan

Anderson

Illing

et al. 2019

HLA

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Adverse drug reactions (ADRs) are a common cause of hospital admissions (up to 19%), with the majority of cases due to off‐target predictable drug effects (type A reactions). However, idiosyncratic drug‐induced immune activated (type B) reactions contribute to a range of hypersensitivity reactions, with T‐cell‐mediated type IV hypersensitivity reactions mainly manifesting as cutaneous ADRs (cADRs). Aromatic antiepileptic drugs (AEDs), used in the treatment of epilepsy as well as bipolar disorder or neuropathic pain, have been implicated as culprit drugs in a spectrum of pathologies ranging from mild maculopapular exanthema (MPE) to severe and life‐threatening conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These AED‐induced cADRs are unpredictable based on pharmacological and clinical factors alone, thereby prompting investigations into genomic contributors mediating risk of pathology. The most strongly associated risk genes identified are from the human leukocyte antigen (HLA) class I alleles, which play a critical role in adaptive immunity by flagging either infected or aberrant cells for recognition by surveying T‐cells. In the setting of drug hypersensitivity, the immunogenicity of HLA molecules and their peptide cargo can be modulated by interactions with small drug molecules that drive inappropriate T‐cell responses. This review discusses the current understanding of HLA class I molecules in modifying risk of AED‐induced cADRs.

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Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

Section: Pharmacogenomic Identification Of Genetic Risk Factors In Aementioning

confidence: 99%

See 1 more Smart Citation

HLA‐associated antiepileptic drug‐induced cutaneous adverse reactions

Mullan

Anderson

Illing

et al. 2019

HLA

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show abstract

“…65–67 Similarly, in South and Southeast Asians, the risk for HLA-B* 15:02-associated IM-ADRs secondary to other aromatic amine anticonvulsants such as phenytoin and lamotrigine is lower than for carbamazepine and oxcarbazepine and HLA associations are unique in Europeans (Table 1). 68 …”

Section: Genetic Associations Of Im-adrsmentioning

confidence: 99%

Severe Delayed Drug Reactions

Pavlos

White

Wanjalla

et al. 2017

Immunology and Allergy Clinics of North America

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“…Recent studies have indicated a significant association between HLA alleles and carbamazepine-induced SJS/TEN in different populations. [8][9][10] A similar investigation remains to be performed in Turkish patients. The frequency of severe eruptions from aromatic antiepileptics suggests a necessity for a genetic investigation in Turkish patients as well, and this is now our future aim.…”

mentioning

confidence: 98%