1932

Abstract

Human leukocyte antigen (HLA) is a hallmark genetic marker for the prediction of certain immune-mediated adverse drug reactions (ADRs). Numerous basic and clinical research studies have provided the evidence base to push forward the clinical implementation of HLA testing for the prevention of such ADRs in susceptible patients. This review explores current translational progress in using HLA as a key susceptibility factor for immune ADRs and highlights gaps in our knowledge. Furthermore, relevant findings of HLA-mediated drug-specific T cell activation are covered, focusing on cellular approaches to link genetic associations to drug-HLA binding as a complementary approach to understand disease pathogenesis.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-052120-014115
2022-01-06
2024-06-23
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/62/1/annurev-pharmtox-052120-014115.html?itemId=/content/journals/10.1146/annurev-pharmtox-052120-014115&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Meng X, Al-Attar Z, Yaseen FS, Jenkins R, Earnshaw C et al. 2017. Definition of the nature and hapten threshold of the β-lactam antigen required for T cell activation in vitro and in patients. J. Immunol. 198:4217–27
    [Google Scholar]
  2. 2. 
    Waddington JC, Meng X, Illing PT, Tailor A, Adair K et al. 2020. Identification of flucloxacillin-haptenated HLA-B*57:01 ligands: evidence of antigen processing and presentation. Toxicol. Sci. 177:454–65
    [Google Scholar]
  3. 3. 
    Callan HE, Jenkins RE, Maggs JL, Lavergne SN, Clarke SE et al. 2009. Multiple adduction reactions of nitroso sulfamethoxazole with cysteinyl residues of peptides and proteins: implications for hapten formation. Chem. Res. Toxicol. 22:937–48
    [Google Scholar]
  4. 4. 
    Alzahrani A, Ogese M, Meng X, Waddington JC, Tailor A et al. 2017. Dapsone and nitroso dapsone activation of naïve T-cells from healthy donors. Chem. Res. Toxicol. 30:2174–86
    [Google Scholar]
  5. 5. 
    Waddington JC, Ali SE, Penman SL, Whitaker P, Hamlett J et al. 2020. Cell membrane transporters facilitate the accumulation of hepatocellular flucloxacillin protein adducts: implication in flucloxacillin-induced liver injury. Chem. Res. Toxicol. 33:2939–43
    [Google Scholar]
  6. 6. 
    Monshi MM, Faulkner L, Gibson A, Jenkins RE, Farrell J et al. 2013. Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury. Hepatology 57:727–39
    [Google Scholar]
  7. 7. 
    Britschgi M, von Greyerz S, Burkhart C, Pichler WJ. 2003. Molecular aspects of drug recognition by specific T cells. Curr. Drug Targets 4:1–11
    [Google Scholar]
  8. 8. 
    Pompeu YA, Stewart JD, Mallal S, Phillips E, Peters B, Ostrov DA. 2012. The structural basis of HLA-associated drug hypersensitivity syndromes. Immunol. Rev. 250:158–66
    [Google Scholar]
  9. 9. 
    Norcross MA, Luo S, Lu L, Boyne MT, Gomarteli M et al. 2012. Abacavir induces loading of novel self-peptides into HLA-B*57:01: an autoimmune model for HLA-associated drug hypersensitivity. AIDS 26:F21–29
    [Google Scholar]
  10. 10. 
    Ostrov DA, Grant BJ, Pompeu YA, Sidney J, Harndahl M et al. 2012. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. PNAS 109:9959–64
    [Google Scholar]
  11. 11. 
    Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z et al. 2012. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486:554–58
    [Google Scholar]
  12. 12. 
    El-Ghaiesh S, Sanderson JP, Farrell J, Lavergne SN, Syn WK et al. 2011. Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways. Chem. Res. Toxicol. 24:791–93
    [Google Scholar]
  13. 13. 
    Usui T, Meng X, Saide K, Farrell J, Thomson P et al. 2017. Characterization of isoniazid-specific T-cell clones in patients with anti-tuberculosis drug-related liver and skin injury. Toxicol. Sci. 155:420–31
    [Google Scholar]
  14. 14. 
    Alfirevic A, Pirmohamed M. 2017. Genomics of adverse drug reactions. Trends. Pharmacol. Sci. 38:100–9
    [Google Scholar]
  15. 15. 
    Pirmohamed M, Ostrov DA, Park BK. 2015. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity. J. Allergy Clin. Immunol. 136:236–44
    [Google Scholar]
  16. 16. 
    Valdes R, Payne DA, Linder MW 2010. Laboratory analysis and application of pharmacogenetics to clinical practice Guidel., Am. Assoc. Clin. Chem. Washington, DC:
    [Google Scholar]
  17. 17. 
    Mallal S, Phillips E, Carosi G, Molina JM, Workman C et al. 2008. HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med. 358:568–79
    [Google Scholar]
  18. 18. 
    Limaye V, Bundell C, Hollingsworth P, Rojana-Udomsart A, Mastaglia F et al. 2015. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve 52:196–203
    [Google Scholar]
  19. 19. 
    Mammen AL, Gaudet D, Brisson D, Christopher-Stine L, Lloyd TE et al. 2012. Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res 64:1233–37
    [Google Scholar]
  20. 20. 
    Sai K, Kajinami K, Akao H, Iwadare M, Sato-Ishida R et al. 2016. A possible role for HLA-DRB1*04:06 in statin-related myopathy in Japanese patients. Drug Metab. Pharmacokinet. 31:467–70
    [Google Scholar]
  21. 21. 
    Lacaze P, Ronaldson KJ, Zhang EJ, Alfirevic A, Shah H et al. 2020. Genetic associations with clozapine-induced myocarditis in patients with schizophrenia. Transl. Psychiatry 10:37
    [Google Scholar]
  22. 22. 
    Nicoletti P, Carr DF, Barrett S, McEvoy L, Friedmann PS et al. 2020. Beta-lactam-induced immediate hypersensitivity reactions: a genome-wide association study of a deeply phenotyped cohort. J. Allergy Clin. Immunol. 147:51830–37.e15
    [Google Scholar]
  23. 23. 
    Krebs K, Bovijn J, Zheng N, Lepamets M, Censin JC et al. 2020. Genome-wide study identifies association between HLA-B*55:01 and self-reported penicillin allergy. Am. J. Hum. Genet. 107:612–21
    [Google Scholar]
  24. 24. 
    Chang WC, Abe R, Anderson P, Anderson W, MR Ardern-Jones et al. 2020. SJS/TEN 2019: from science to translation. J. Dermatol. Sci. 98:2–12
    [Google Scholar]
  25. 25. 
    Saokaew S, Tassaneeyakul W, Maenthaisong R, Chaiyakunapruk N. 2014. Cost-effectiveness analysis of HLA-B*5801 testing in preventing allopurinol-induced SJS/TEN in Thai population. PLOS ONE 9:e94294
    [Google Scholar]
  26. 26. 
    Park D-J, Kang J-H, Lee J-W, Lee K-E, Wen L et al. 2015. Cost-effectiveness analysis of HLA–B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea. Arthritis Care Res 67:280–87
    [Google Scholar]
  27. 27. 
    Ke CH, Chung WH, Wen YH, Huang YB, Chuang HY et al. 2017. Cost-effectiveness analysis for genotyping before allopurinol treatment to prevent severe cutaneous adverse drug reactions. J. Rheumatol. 44:835–43
    [Google Scholar]
  28. 28. 
    Plumpton CO, Alfirevic A, Pirmohamed M, Hughes DA. 2017. Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout. Rheumatology 56:1729–39
    [Google Scholar]
  29. 29. 
    Chong HY, Lim YH, Prawjaeng J, Tassaneeyakul W, Mohamed Z, Chaiyakunapruk N 2018. Cost-effectiveness analysis of HLA-B*58:01 genetic testing before initiation of allopurinol therapy to prevent allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in a Malaysian population. Pharmacogenet. Genom. 28:56–67
    [Google Scholar]
  30. 30. 
    Dong D, Tan-Koi WC, Teng GG, Finkelstein E, Sung C. 2015. Cost-effectiveness analysis of genotyping for HLA-B*5801 and an enhanced safety program in gout patients starting allopurinol in Singapore. Pharmacogenomics 16:1781–93
    [Google Scholar]
  31. 31. 
    Pruis SL, Jeon YK, Pearce F, Thong BY, Aziz MIA. 2020. Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore. J. Med. Econ. 23:838–47
    [Google Scholar]
  32. 32. 
    Plumpton CO, Roberts D, Pirmohamed M, Hughes DA. 2016. A systematic review of economic evaluations of pharmacogenetic testing for prevention of adverse drug reactions. PharmacoEconomics 34:771–93
    [Google Scholar]
  33. 33. 
    Dong D, Sung C, Finkelstein EA. 2012. Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology 79:1259–67
    [Google Scholar]
  34. 34. 
    Chong HY, Mohamed Z, Tan LL, Wu DBC, Shabaruddin FH et al. 2017. Is universal HLA-B*15:02 screening a cost-effective option in an ethnically diverse population? A case study of Malaysia. Br. J. Dermatol. 177:1102–12
    [Google Scholar]
  35. 35. 
    Jaruthamsophon K, Tipmanee V, Sangiemchoey A, Sukasem C, Limprasert P. 2017. HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis. Sci. Rep. 7:45553
    [Google Scholar]
  36. 36. 
    Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S et al. 2014. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin. Pharmacol. Ther. 96:542–48
    [Google Scholar]
  37. 37. 
    Liu H, Wang Z, Bao F, Wang C, Sun L et al. 2019. Evaluation of prospective HLA-B*13:01 screening to prevent dapsone hypersensitivity syndrome in patients with leprosy. JAMA Dermatol 155:666–72
    [Google Scholar]
  38. 38. 
    KNMP 2020. Pharmacogenetic recommendations. Guidel., Dutch Pharmacogenetic Work. Group, KNMP The Hague, Neth:.
    [Google Scholar]
  39. 39. 
    Girardin FR, Poncet A, Perrier A, Vernaz N, Pletscher M et al. 2019. Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine. Pharmacogenomics J 19:211–18
    [Google Scholar]
  40. 40. 
    Naisbitt DJ, Olsson-Brown A, Gibson A, Meng X, Ogese MO et al. 2020. Immune dysregulation increases the incidence of delayed-type drug hypersensitivity reactions. Allergy 75:781–97
    [Google Scholar]
  41. 41. 
    Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I et al. 2009. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat. Genet. 41:816–19
    [Google Scholar]
  42. 42. 
    Alfirevic A, Pirmohamed M. 2012. Predictive genetic testing for drug-induced liver injury: considerations of clinical utility. Clin. Pharmacol. Ther. 92:376–80
    [Google Scholar]
  43. 43. 
    Pavlos R, Deshpande P, Chopra A, Leary S, Strautins K et al. 2020. New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals. Hum. Immunol. 81:300–4
    [Google Scholar]
  44. 44. 
    Gonzalez-Galarza FF, McCabe A, Santos E, Jones J, Takeshita L et al. 2020. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucleic Acids Res 48:D783–88
    [Google Scholar]
  45. 45. 
    Hung SI, Chung WH, Jee SH, Chen WC, Chang YT et al. 2006. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet. Genom. 16:297–306
    [Google Scholar]
  46. 46. 
    Hsiao YH, Hui RC, Wu T, Chang WC, Hsih MS et al. 2014. Genotype-phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: strength and clinical correlations. J. Dermatol. Sci. 73:101–9
    [Google Scholar]
  47. 47. 
    Wang Q, Sun S, Xie M, Zhao K, Li X, Zhao Z. 2017. Association between the HLA-B alleles and carbamazepine-induced SJS/TEN: a meta-analysis. Epilepsy Res 135:19–28
    [Google Scholar]
  48. 48. 
    Li LJ, Hu FY, Wu XT, An DM, Yan B, Zhou D 2013. Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese. Epilepsy Res 106:296–300
    [Google Scholar]
  49. 49. 
    Moon J, Park HK, Chu K, Sunwoo JS, Byun JI et al. 2015. The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. Epilepsia 56:e161–67
    [Google Scholar]
  50. 50. 
    Deng Y, Li S, Zhang L, Jin H, Zou X 2018. Association between HLA alleles and lamotrigine-induced cutaneous adverse drug reactions in Asian populations: a meta-analysis. Seizure 60:163–71
    [Google Scholar]
  51. 51. 
    Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP et al. 2011. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 141:338–47
    [Google Scholar]
  52. 52. 
    Hautekeete ML, Horsmans Y, Van Waeyenberge C, Demanet C, Henrion J et al. 1999. HLA association of amoxicillin-clavulanate–induced hepatitis. Gastroenterology 117:1181–86
    [Google Scholar]
  53. 53. 
    O'Donohue J, Oien KA, Donaldson P, Underhill J, Clare M et al. 2000. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut 47:717–20
    [Google Scholar]
  54. 54. 
    McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperaviciute D et al. 2011. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N. Engl. J. Med. 364:1134–43
    [Google Scholar]
  55. 55. 
    Lichtenfels M, Farrell J, Ogese MO, Bell CC, Eckle S et al. 2014. HLA restriction of carbamazepine-specific T-cell clones from an HLA-A*31:01-positive hypersensitive patient. Chem. Res. Toxicol. 27:175–77
    [Google Scholar]
  56. 56. 
    Karnes JH, Rettie AE, Somogyi AA, Huddart R, Fohner AE et al. 2021. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and HLA-B genotypes and phenytoin dosing: 2020 update. Clin. Pharmacol. Ther. 109:302–9
    [Google Scholar]
  57. 57. 
    He XJ, Jian LY, He XL, Tang M, Wu Y et al. 2014. Association of ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms with the risk of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Chinese Han patients with epilepsy. Epilepsia 55:1301–6
    [Google Scholar]
  58. 58. 
    Yip VLM, Pertinez H, Meng X, Maggs JL, Carr DF et al. 2020. Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine. Br. J. Clin. Pharmacol. 87:62572–88
    [Google Scholar]
  59. 59. 
    Carr DF, Bourgeois S, Chaponda M, Takeshita LY, Morris AP et al. 2017. Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population. J. Antimicrob. Chemother. 72:1152–62
    [Google Scholar]
  60. 60. 
    Zhang FR, Liu H, Irwanto A, Fu XA, Li Y et al. 2013. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N. Engl. J. Med. 369:1620–28
    [Google Scholar]
  61. 61. 
    Tempark T, Satapornpong P, Rerknimitr P, Nakkam N, Saksit N et al. 2017. Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13:01 allele in the Thai population. Pharmacogenet. Genom. 27:429–37
    [Google Scholar]
  62. 62. 
    Sukasem C, Chaichan C, Nakkrut T, Satapornpong P, Jaruthamsophon K et al. 2018. Association between HLA-B alleles and carbamazepine-induced maculopapular exanthema and severe cutaneous reactions in Thai patients. J. Immunol. Res. 2018.2780272
    [Google Scholar]
  63. 63. 
    Xu CF, Johnson T, Wang X, Carpenter C, Graves AP et al. 2016. HLA-B*57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer. Clin. Cancer Res. 22:1371–77
    [Google Scholar]
  64. 64. 
    Nicoletti P, Barrett S, McEvoy L, Daly AK, Aithal G et al. 2019. Shared genetic risk factors across carbamazepine-induced hypersensitivity reactions. Clin. Pharmacol. Ther. 106:1028–36
    [Google Scholar]
  65. 65. 
    Naisbitt DJ, Britschgi M, Wong G, Farrell J, Depta JP et al. 2003. Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Mol. Pharmacol. 63:732–41
    [Google Scholar]
  66. 66. 
    Wu Y, Sanderson JP, Farrell J, Drummond NS, Hanson A et al. 2006. Activation of T cells by carbamazepine and carbamazepine metabolites. J. Allergy Clin. Immunol. 118:233–41
    [Google Scholar]
  67. 67. 
    Tailor A, Meng X, Adair K, Farrell J, Waddington JC et al. 2020. HLA DRB1*15:01-DQB1*06:02-restricted human CD4+ T cells are selectively activated with amoxicillin-peptide adducts. Toxicol. Sci 178:115–26
    [Google Scholar]
  68. 68. 
    Lavergne SN, Whitaker P, Peckham D, Conway S, Park BK, Naisbitt DJ. 2010. Drug metabolite-specific lymphocyte responses in sulfamethoxazole allergic patients with cystic fibrosis. Chem. Res. Toxicol. 23:1009–11
    [Google Scholar]
  69. 69. 
    Kongpan T, Mahasirimongkol S, Konyoung P, Kanjanawart S, Chumworathayi P et al. 2015. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet. Genom. 25:402–11
    [Google Scholar]
  70. 70. 
    Sukasem C, Pratoomwun J, Satapornpong P, Klaewsongkram J, Rerkpattanapipat T et al. 2020. Genetic association of co-trimoxazole-induced severe cutaneous adverse reactions is phenotype-specific: HLA class I genotypes and haplotypes. Clin. Pharmacol. Ther. 108:1078–89
    [Google Scholar]
  71. 71. 
    Wang CW, Tassaneeyakul W, Chen CB, Chen WT, Teng YC et al. 2020. Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians. J. Allergy Clin. Immunol. 147:41402–12
    [Google Scholar]
  72. 72. 
    Thomson PJ, Illing PT, Farrell J, Alhaidari M, Bell CC et al. 2020. Modification of the cyclopropyl moiety of abacavir provides insight into the structure activity relationship between HLA-B*57:01 binding and T-cell activation. Allergy 75:636–47
    [Google Scholar]
  73. 73. 
    Zhao Q, Alhilali K, Alzahrani A, Almutairi M, Amjad J et al. 2019. Dapsone- and nitroso dapsone-specific activation of T cells from hypersensitive patients expressing the risk allele HLA-B*13:01. Allergy 74:1533–48
    [Google Scholar]
  74. 74. 
    Ogese MO, Saide K, Faulkner L, Whitaker P, Peckham D et al. 2015. HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4-positive T lymphocytes from patients with cystic fibrosis. Clin. Exp. Allergy 45:1305–16
    [Google Scholar]
  75. 75. 
    Kim SH, Saide K, Farrell J, Faulkner L, Tailor A et al. 2015. Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury. Hepatology 62:887–99
    [Google Scholar]
  76. 76. 
    Ariza A, Fernández-Santamaría R, Meng X, Salas M, Ogese MO et al. 2020. Characterization of amoxicillin and clavulanic acid specific T-cell clones from patients with immediate drug hypersensitivity. Allergy 75:2562–73
    [Google Scholar]
  77. 77. 
    Ko TM, Chung WH, Wei CY, Shih HY, Chen JK et al. 2011. Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. J. Allergy Clin. Immunol. 128:1266–76.e11
    [Google Scholar]
  78. 78. 
    Ko TM, Chen YT. 2012. T-cell receptor and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: understanding a hypersensitivity reaction. Expert Rev. Clin. Immunol. 8:467–77
    [Google Scholar]
  79. 79. 
    Kim D, Kobayashi T, Voisin B, Jo JH, Sakamoto K et al. 2020. Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report. Nat. Med. 26:236–43
    [Google Scholar]
  80. 80. 
    Whitaker P, Naisbitt D, Peckham D. 2012. Nonimmediate β-lactam reactions in patients with cystic fibrosis. Curr. Opin. Allergy Clin. Immunol. 12:369–75
    [Google Scholar]
  81. 81. 
    Raschi E, Antonazzo IC, La Placa M, Ardizzoni A, Poluzzi E, De Ponti F 2019. Serious cutaneous toxicities with immune checkpoint inhibitors in the U.S. Food and Drug Administration adverse event reporting system. Oncologist 24:e1228–31
    [Google Scholar]
  82. 82. 
    Gibson A, Ogese M, Sullivan A, Wang E, Saide K et al. 2014. Negative regulation by PD-L1 during drug-specific priming of IL-22-secreting T cells and the influence of PD-1 on effector T cell function. J. Immunol. 192:2611–21
    [Google Scholar]
  83. 83. 
    Gibson A, Faulkner L, Lichtenfels M, Ogese M, Al-Attar Z et al. 2017. The effect of inhibitory signals on the priming of drug hapten-specific T cells that express distinct Vβ receptors. J. Immunol. 199:1223–37
    [Google Scholar]
  84. 84. 
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M et al. 2005. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. PNAS 102:4134–39
    [Google Scholar]
  85. 85. 
    Shim JS, Yun J, Kim MY, Chung SJ, Oh JH et al. 2019. The presence of HLA-B75, DR13 homozygosity, or DR14 additionally increases the risk of allopurinol-induced severe cutaneous adverse reactions in HLA-B*58:01 carriers. J. Allergy Clin. Immunol. Pract. 7:1261–70
    [Google Scholar]
  86. 86. 
    Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M et al. 2011. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum. Mol. Genet. 20:1034–41
    [Google Scholar]
  87. 87. 
    Capule F, Tragulpiankit P, Mahasirimongkol S, Jittikoon J, Wichukchinda N et al. 2020. Association of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients. Pharmacogenomics J 20:533–41
    [Google Scholar]
  88. 88. 
    He XJ, Jian LY, He XL, Wu Y, Xu YY et al. 2013. Association between the HLA-B*15:02 allele and carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han individuals of northeastern China. Pharmacol. Rep. 65:1256–62
    [Google Scholar]
  89. 89. 
    Shi YW, Min FL, Zhou D, Qin B, Wang J et al. 2017. HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology 88:2183–91
    [Google Scholar]
  90. 90. 
    Ihtisham K, Ramanujam B, Srivastava S, Mehra NK, Kaur G et al. 2019. Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population. Seizure 66:99–103
    [Google Scholar]
  91. 91. 
    Pirmohamed M, Lin K, Chadwick D, Park BK 2001. TNFα promoter region gene polymorphisms in carbamazepine-hypersensitive patients. Neurology 56:890–96
    [Google Scholar]
  92. 92. 
    Alfirevic A, Mills T, Harrington P, Pinel T, Sherwood J et al. 2006. Serious carbamazepine-induced hypersensitivity reactions associated with the HSP70 gene cluster. Pharmacogenet. Genom. 16:287–96
    [Google Scholar]
  93. 93. 
    Ciccacci C, Politi C, Mancinelli S, Ciccacci F, Lucaroni F et al. 2018. A multivariate genetic analysis confirms rs5010528 in the human leucocyte antigen-C locus as a significant contributor to Stevens-Johnson syndrome/toxic epidermal necrolysis susceptibility in a Mozambique HIV population treated with nevirapine. J. Antimicrob. Chemother. 73:2137–40
    [Google Scholar]
  94. 94. 
    Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS et al. 2010. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 11:349–56
    [Google Scholar]
  95. 95. 
    Tassaneeyakul W, Prabmeechai N, Sukasem C, Kongpan T, Konyoung P et al. 2016. Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population. Pharmacogenet. Genom. 26:225–34
    [Google Scholar]
  96. 96. 
    Mallal S, Nolan D, Witt C, Masel G, Martin AM et al. 2002. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359:727–32
    [Google Scholar]
  97. 97. 
    Yuan J, Guo S, Hall D, Cammett AM, Jayadev S et al. 2011. Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent. AIDS 25:1271–80
    [Google Scholar]
  98. 98. 
    Chantarangsu S, Mushiroda T, Mahasirimongkol S, Kiertiburanakul S, Sungkanuparph S et al. 2011. Genome-wide association study identifies variations in 6p21.3 associated with nevirapine-induced rash. Clin. Infect. Dis. 53:341–48
    [Google Scholar]
  99. 99. 
    Phillips E, Bartlett JA, Sanne I, Lederman MM, Hinkle J et al. 2013. Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa. J. Acquir. Immune Defic. Syndr. 1999. 62:e55–57
    [Google Scholar]
  100. 100. 
    Hirata K, Takagi H, Yamamoto M, Matsumoto T, Nishiya T et al. 2008. Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J 8:29–33
    [Google Scholar]
  101. 101. 
    Ariyoshi N, Iga Y, Hirata K, Sato Y, Miura G et al. 2010. Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese. Drug Metab. Pharmacokinet. 25:298–306
    [Google Scholar]
  102. 102. 
    Goldstein JI, Jarskog LF, Hilliard C, Alfirevic A, Duncan L et al. 2014. Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. Nat. Commun. 5:4757
    [Google Scholar]
  103. 103. 
    Dettling M, Cascorbi I, Opgen-Rhein C, Schaub R. 2007. Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. Pharmacogenomics J 7:325–32
    [Google Scholar]
  104. 104. 
    Oussalah A, Mayorga C, Blanca M, Barbaud A, Nakonechna A et al. 2016. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review. Allergy 71:443–62
    [Google Scholar]
  105. 105. 
    Donaldson PT, Daly AK, Henderson J, Graham J, Pirmohamed M et al. 2010. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J. Hepatol. 53:1049–53
    [Google Scholar]
  106. 106. 
    Alfirevic A, Jorgensen AL, Williamson PR, Chadwick DW, Park BK, Pirmohamed M. 2006. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics 7:813–18
    [Google Scholar]
  107. 107. 
    Nguyen DV, Chu HC, Nguyen DV, Phan MH, Craig T et al. 2015. HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese. Asia Pac. Allergy 5:68–77
    [Google Scholar]
  108. 108. 
    Moon J, Kim TJ, Lim JA, Sunwoo JS, Byun JI et al. 2016. HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. Epilepsia 57:1879–86
    [Google Scholar]
  109. 109. 
    Farrell J, Lichtenfels M, Sullivan A, Elliott EC, Alfirevic A et al. 2013. Activation of carbamazepine-responsive T-cell clones with metabolically inert halogenated derivatives. J. Allergy Clin. Immunol. 132:493–95
    [Google Scholar]
  110. 110. 
    Wu Y, Farrell J, Pirmohamed M, Park BK, Naisbitt DJ. 2007. Generation and characterization of antigen-specific CD4+, CD8+, and CD4+CD8+ T-cell clones from patients with carbamazepine hypersensitivity. J. Allergy Clin. Immunol. 119:973–81
    [Google Scholar]
  111. 111. 
    Naisbitt DJ, Farrell J, Wong G, Depta JP, Dodd CC et al. 2003. Characterization of drug-specific T cells in lamotrigine hypersensitivity. J. Allergy Clin. Immunol. 111:1393–403
    [Google Scholar]
  112. 112. 
    Castrejon JL, Berry N, El-Ghaiesh S, Gerber B, Pichler WJ et al. 2010. Stimulation of human T cells with sulfonamides and sulfonamide metabolites. J. Allergy Clin. Immunol. 125:411–18.e4
    [Google Scholar]
  113. 113. 
    von Greyerz S, Zanni MP, Frutig K, Schnyder B, Burkhart C, Pichler WJ. 1999. Interaction of sulfonamide derivatives with the TCR of sulfamethoxazole-specific human αβ+ T cell clones. J. Immunol. 162:595–602
    [Google Scholar]
  114. 114. 
    Tailor A, Waddington JC, Hamlett J, Maggs J, Kafu L et al. 2019. Definition of haptens derived from sulfamethoxazole: in vitro and in vivo. Chem. Res. Toxicol. 32:2095–106
    [Google Scholar]
  115. 115. 
    Yun J, Marcaida MJ, Eriksson KK, Jamin H, Fontana S et al. 2014. Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01. J. Immunol. 192:2984–93
    [Google Scholar]
  116. 116. 
    Bell CC, Faulkner L, Martinsson K, Farrell J, Alfirevic A et al. 2013. T-cells from HLA-B*57:01+ human subjects are activated with abacavir through two independent pathways and induce cell death by multiple mechanisms. Chem. Res. Toxicol. 26:759–66
    [Google Scholar]
  117. 117. 
    Usui T, Faulkner L, Farrell J, French NS, Alfirevic A et al. 2018. Application of in vitro T cell assay using human leukocyte antigen-typed healthy donors for the assessment of drug immunogenicity. Chem. Res. Toxicol. 31:165–67
    [Google Scholar]
  118. 118. 
    Meng X, Earnshaw CJ, Tailor A, Jenkins RE, Waddington JC et al. 2016. Amoxicillin and clavulanate form chemically and immunologically distinct multiple haptenic structures in patients. Chem. Res. Toxicol. 29:1762–72
    [Google Scholar]
  119. 119. 
    Ogese MO, Lister A, Jenkins RE, Meng X, Alfirevic A et al. 2020. Characterization of clozapine-responsive human T cells. J. Immunol. 205:2375–90
    [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-052120-014115
Loading
/content/journals/10.1146/annurev-pharmtox-052120-014115
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error