RESUMEN
HLA-B*15:679 and HLA-C*15:02:01:61 differ from HLA-B*15:12:01 and HLA-C*15:02:01:01 by a single nucleotides.
Asunto(s)
Alelos , Secuencia de Bases , Antígenos HLA-C , Prueba de Histocompatibilidad , Humanos , Antígenos HLA-C/genética , India , Exones , Análisis de Secuencia de ADN/métodos , Polimorfismo de Nucleótido Simple , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Alineación de Secuencia , CodónRESUMEN
Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers-HLA-B*15:11 and HLA-B*15:21-which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%-100.00%) and a specificity of 100% (95% confidence interval = 95.07%-100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.
Asunto(s)
Carbamazepina , Antígeno HLA-B15 , Humanos , Carbamazepina/efectos adversos , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Tailandia , Anticonvulsivantes/efectos adversos , Pueblo Asiatico/genética , Farmacogenética , Serogrupo , Sensibilidad y Especificidad , AlelosRESUMEN
HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Asunto(s)
Exones , Antígeno HLA-B15 , Prueba de Histocompatibilidad , Humanos , Alelos , Secuencia de Bases , Codón , Pueblos del Este de Asia , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Alineación de Secuencia , Análisis de Secuencia de ADN/métodosRESUMEN
HLA-B*15:659 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Asunto(s)
Alelos , Pueblo Asiatico , Secuencia de Bases , Exones , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Pueblo Asiatico/genética , Análisis de Secuencia de ADN/métodos , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Alineación de Secuencia , Codón , Donantes de Tejidos , Pueblos del Este de AsiaRESUMEN
Genetic differences among individuals could affect the clinical presentations and outcomes of COVID-19. Human Leukocyte Antigens are associated with COVID-19 susceptibility, severity, and prognosis. This study aimed to identify HLA-B and -C genotypes among 69 Egyptian patients with COVID-19 and correlate them with disease outcomes and other clinical and laboratory data. HLA-B and -C typing was performed using Luminex-based HLA typing kits. Forty patients (58%) had severe COVID-19; 55% of these patients died, without reported mortality in the moderate group. The alleles associated with severe COVID-19 were HLA-B*41, -B*42, -C*16, and -C*17, whereas HLA-B*15, -C*7, and -C*12 were significantly associated with protection against mortality. Regression analysis showed that HLA-B*15 was the only allele associated with predicted protection against mortality, where the likelihood of survival increased with HLA-B*15 (P < 0.001). Patient survival was less likely to occur with higher total leukocytic count, ferritin, and creatinine levels. This study provides interesting insights into the association between HLA class I alleles and protection from or severity of COVID-19 through immune response modulation. This is the first study to investigate this relationship in Egyptian patients. More studies are needed to understand how HLA class I alleles interact and affect Cytotoxic T lymphocytes and natural killer cell function.
Asunto(s)
COVID-19/genética , Antígeno HLA-B15/genética , SARS-CoV-2/patogenicidad , Anciano , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/virología , Egipto , Femenino , Predisposición Genética a la Enfermedad , Antígeno HLA-B15/inmunología , Haplotipos , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores Protectores , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
OBJECTIVE: To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA). METHODS: 104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in ERAP1, and rs2910686, rs2248374 and rs2549782 in ERAP2. RESULTS: 70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively. CONCLUSION: An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.
Asunto(s)
Aminopeptidasas/genética , Predisposición Genética a la Enfermedad , Antígeno HLA-B15/genética , Antígeno HLA-B27/genética , Polimorfismo de Nucleótido Simple , Espondiloartritis/diagnóstico , Espondiloartritis/etiología , Adulto , Alelos , Autoinmunidad , Biomarcadores/sangre , Biomarcadores/metabolismo , Colombia , Citocinas/sangre , Citocinas/metabolismo , Femenino , Estudios de Asociación Genética , Genotipo , Antígeno HLA-B15/inmunología , Antígeno HLA-B27/inmunología , Prueba de Histocompatibilidad , Humanos , Mediadores de Inflamación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fenotipo , Radiografía , Espondiloartritis/metabolismoRESUMEN
The HLA-B15 typing by serological approaches defined the serological subgroups (or splits) B62, B63, B75, B76, B77 and B70 (B71 and B72). The scarcity of sera with specific anti-HLA antibodies makes the serological typing method difficult to discriminate a high variety of HLA antigens, especially between the B15 antigen subgroups. Advancements in DNA-based technologies have led to a switch from serological typing to high-resolution DNA typing methods. DNA sequencing techniques assign B15 specificity to all alleles in the HLA-B*15 allele group, without distinction of the serological split equivalents. However, the presence of antibodies in the patient defined as split B15 antigens urges the identification of HLA-B*15 allele subtypes of the donor, since the presence of donor-specific antibodies is an important contraindication for organ transplantation. Although the HLA dictionary comprises information regarding the serological subtypes of HLA alleles, there are currently 394 B15 antigens out of 516 in the IPD-IMGT/HLA database (3.38.0) without any assigned serological subtype. In this regard, we aimed to identify specific amino acid patterns for each B*15 serological split, in order to facilitate the assignment of B*15 alleles to serological equivalents after high-resolution molecular typing. As a result, serological specificities of 372/394 not yet assigned alleles could be predicted based on amino acid motifs. Furthermore, two new serological types were identified and added, B62-Bw4 and B71-Bw4.
Asunto(s)
Dermatoglifia del ADN/métodos , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Prueba de Histocompatibilidad/métodos , Linfocitos/inmunología , Donantes de Tejidos , Alelos , Secuencias de Aminoácidos , Antígeno HLA-B15/sangre , Antígeno HLA-B15/clasificación , HumanosRESUMEN
We report a discordance between complement-dependent cytotoxicity and next-generation sequencing molecular typing revealing HLA-B*15:47:01 allele with undefined serological equivalent confirmed by high-level immunization against the B15 serotype. Due to the high-level immunization against HLA-B15 and B70 antigens, we considered the HLA-B*15:47:01 allele to be B Blank and not as B15 or B70 serological specificity.
Asunto(s)
Genes MHC Clase I/genética , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Alelos , Antígeno B7-2/inmunología , Proteínas del Sistema Complemento/metabolismo , Citotoxicidad Inmunológica , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αßTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αßTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αßTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
Asunto(s)
Carbamazepina/efectos adversos , Complejo Receptor-CD3 del Antígeno de Linfocito T/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Síndrome de Stevens-Johnson/inmunología , Linfocitos T Citotóxicos/inmunología , Traslado Adoptivo , Adulto , Anciano , Animales , Modelos Animales de Enfermedad , Femenino , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Humanos , Masculino , Ratones Transgénicos , Persona de Mediana Edad , Complejo Receptor-CD3 del Antígeno de Linfocito T/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/patología , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/patología , Linfocitos T Citotóxicos/metabolismo , Linfocitos T Citotóxicos/trasplanteRESUMEN
Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell-mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.
Asunto(s)
Antígenos HLA-B , Antígeno HLA-B15 , Síndrome de Stevens-Johnson , Animales , Pueblo Asiatico , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Didesoxinucleósidos/efectos adversos , Didesoxinucleósidos/uso terapéutico , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Humanos , Pruebas Cutáneas/normas , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/inmunología , Síndrome de Stevens-Johnson/patologíaRESUMEN
HLA-B*15:476 differs from HLA-B*15:01:01:01 by one nucleotide substitution at codon 299 in exon 5.
Asunto(s)
Alelos , Sustitución de Aminoácidos , Exones , Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B15/inmunología , Trasplante de Corazón , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN , Receptores de TrasplantesRESUMEN
HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/µL. The unit cost of this assay is less than $5 USD with total time of 110 minutes.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/genética , Antígenos HLA-A/genética , Antígeno HLA-B15/genética , Reacción en Cadena de la Polimerasa Multiplex/métodos , Síndrome de Stevens-Johnson/genética , Alelos , Secuencia de Bases , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Expresión Génica , Predisposición Genética a la Enfermedad , Antígenos HLA-A/inmunología , Antígeno HLA-B15/inmunología , Humanos , Límite de Detección , Reacción en Cadena de la Polimerasa Multiplex/economía , Reproducibilidad de los Resultados , Alineación de Secuencia , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/inmunologíaRESUMEN
T-cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best-suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. We generated an MHC cell library and developed a platform approach to detect, isolate, and re-express TCRs specific for immunodominant pMHCs. The platform approach was applied to identify a human papillomavirus (HPV16) oncogene E5-specific TCR, recognizing a novel, naturally processed pMHC (HLA-B*15:01) and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*07:02). The platform provides a useful tool to isolate in an unbiased manner TCRs specific for novel and immunodominant pMHC targets for use in TCR immunotherapy.
Asunto(s)
Traslado Adoptivo/métodos , Antígeno HLA-B15 , Antígeno HLA-B7 , Neoplasias , Péptidos/inmunología , Receptores de Antígenos de Linfocitos T , Linfocitos T/inmunología , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Antígeno HLA-B7/genética , Antígeno HLA-B7/inmunología , Humanos , Células K562 , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Péptidos/genética , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
We report the full-length sequences of 4 alleles of the HLA-B*15 gene family.
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo Genético , Donantes de Tejidos , Pueblo Asiatico , Secuencia de Bases , Clonación Molecular , Codón/química , Expresión Génica , Antígeno HLA-B15/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Intrones , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
We report the full-length sequence of 4 HLA-B*15 alleles, B*15:07:01:01, B*15:27:01, B*15:32:01 and B*15:58.
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo Genético , Donantes de Tejidos , Pueblo Asiatico , Secuencia de Bases , Clonación Molecular , Codón/química , Expresión Génica , Antígeno HLA-B15/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Intrones , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
HLA-B*15:01:23 has 1 synonymous nucleotide change from HLA-B*15:01:01:01 at nucleotide 393 (codon 107 glycine).
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B15/inmunología , Prueba de Histocompatibilidad , Humanos , Transfusión de Plaquetas , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
The novel HLA-B*15:416 allele differs from HLA-B*15:01:01:01 by a single nucleotide substitution at codon 114.
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Sustitución de Aminoácidos , Secuencia de Bases , Trasplante de Médula Ósea , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B15/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
One nucleotide replacement at residue 221 of HLA-B*15:18:01:01 results in a new allele, HLA-B*15:414.
Asunto(s)
Alelos , Exones , Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Sustitución de Aminoácidos , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B15/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN , TaiwánRESUMEN
BACKGROUND: HLA-B*15:02 is a known biomarker for carbamazepine (CBZ)-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some ethnic populations. The US FDA recommends B*15:02 screening for Asian and other populations with a high prevalence of B*15:02 prior to treatment with CBZ to prevent drug-related SJS/TEN. MATERIALS AND METHODS: A total of 1607 blood samples were collected from volunteer blood donors who were ethnic minorities living in the Yunnan province of southwestern China, including 153 Yi, 193 Naxi, 167 Miao, 156 Lisu, 166 Derung, 211 Bai, 184 Hani, 198 Dai, and 179 Zhuang. The genetic diversity of the HLA-B*15:02 genes in the ethnic minority samples was examined using sequence based typing at high resolution. RESULTS: The allele frequencies of HLA-B*15:02 in the Yi, Naxi, Miao, Lisu, Derung, Bai, Hani, Dai, and Zhuang populations were 4.25%, 4.4%, 5.09%, 5.77%, 6.33%, 7.82%, 8.15%, 9.6%, and 15.36%, respectively. The frequencies of HLA-B*15:02 carriers in the Yi, Naxi, Miao, Lisu, Derung, Bai, Hani, Dai, and Zhuang populations were 8.5%, 8.8%, 9.58%, 10.9%, 12.65%, 15.64%, 16.3%, 18.69%, and 28.49%, respectively. CONCLUSION: The HLA-B*15:02 allele frequencies indicated that the prevalence of B*15:02 was different among the different ethnic populations. Because the number of carriers of B*15:02 was high in some ethnic populations, larger studies are required to confirm these findings. The Zhuang population had the highest frequency of B*15:02 in this study. More attention should be paid to CBZ-induced SJS/TEN in Chinese minority populations.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígeno HLA-B15/genética , Síndrome de Stevens-Johnson/genética , Adulto , Alelos , Pueblo Asiatico , Donantes de Sangre , China/etnología , Contraindicaciones de los Medicamentos , Etnicidad , Femenino , Expresión Génica , Variación Genética , Antígeno HLA-B15/inmunología , Humanos , Masculino , Síndrome de Stevens-Johnson/etnología , Síndrome de Stevens-Johnson/inmunología , Síndrome de Stevens-Johnson/prevención & controlRESUMEN
Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.