HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies

Fernandez, Christian A.; Smith, Colton; Yang, Wenjian; Date, M.; Bashford, Donald; Larsen, Eric; Bowman, W. Paul; Liu, Chengcheng; Ramsey, Laura B.; Chang, Tamara; Turner, Victoria; Loh, Mignon L.; Raetz, Elizabeth A.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Önengüt-Gümüşcü, Suna; Chen, Wei Min; Concannon, Patrick; Rich, Stephen S.; Scheet, Paul; Jeha, Sima; Pui, Ching Hon; Evans, William E.; Devidas, Meenakshi; Relling, Mary V.

doi:10.1182/blood-2014-03-563742

Cited by 94 publications

(90 citation statements)

References 77 publications

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“…HLA-B*5801 were reported to be associated with allopurinol-induced Stevens-Johnson syndrome or drug-induced hypersensitivity syndrome (39,40), and HLA-B*5701 were reported to be associated with abacavir-induced hypersensitivity reaction (41,42). There were also a few studies showing an association between HLA II alleles and drug allergy; for instance, HLA-DRB1*0701 was related to asparaginase allergy in people of European descent (43), and HLA-DRB9 was related to penicillin-induced immediate hypersensitive reaction in Chinese Han populations (44). In the current study, haplotype HLA-QA1*0104/DQB1*0503/DRB1*1405 presented a much higher frequency in both D-ATIN (58%) and TINU syndrome (43.5%) patients than it had in healthy controls (7.5%).…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study

Jia

et al. 2018

The Journal of Immunology

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Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various origins. HLA-DQA1, -DQB1, and -DRB1 have been associated with development of tubulointerstitial nephritis and uveitis (TINU) syndrome in case reports and small case series, but information about HLA genetic susceptibility to drug hypersensitivity–related ATIN (D-ATIN) or other types of ATIN is limited. In this article, we genotyped 154 patients with ATIN of different causes and 200 healthy controls at HLA-DQA1, -DQB1, and -DRB1 loci. We found that there was no difference between patients with D-ATIN and TINU in the carrier’s frequency of HLA-DQA1, -DQB1, or -DRB1. Patients with Sjogren’s syndrome–ATIN and IgG4-related ATIN presented a different pattern of tested HLA alleles. HLA-DQA1*0104 (p value corrected by false discovery rate method [Pc] = 4.72 × 10−22, odds ratio [OR] = 13.81), -DQB1*0503 (Pc = 1.95 × 10−14, OR = 9.51), and -DRB1*1405 (Pc = 8.06 × 10−19, OR = 12.80) were significant risk alleles for the occurrence of D-ATIN and TINU. There were no significant associations between tested HLA alleles and ATIN induced by other causes. Patients with D-ATIN/TINU carrying HLA-DQA1*0104/DQB1*0503/DRB1*1405 had higher peak serum creatinine and more severe renal tubulointerstitial inflammatory impairment. They also had significantly higher levels of tubular HLA-DR and HLA-DQ expression, which were correlated with the numbers of interstitial CD4+ T lymphocytes (r = 0.975, p < 0.001 and r = 0.832, p = 0.005, respectively) and monocytes/macrophages (r = 0.721, p = 0.004 and r = 0.615, p = 0.02, respectively). In conclusion, patients with D-ATIN or TINU have genetic susceptibility in HLA-DQA1, -DQB1, and -DRB1 alleles. HLA-DQA1*0104/DQB1*0503/DRB1*1405 serves as a significant risk haplotype for development of D-ATIN and TINU, which might facilitate renal tubulointerstitial inflammation by enhancing Ag-presenting capacity of renal tubular cells.

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Section: Discussionmentioning

confidence: 99%

HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study

Jia

et al. 2018

The Journal of Immunology

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“…To date, only 10 pharmacogenetics studies analyzing L-ASP have been performed in pediatric ALL [34,[41][42][43][44][45][46][47][48][49]. Among them, six specifically focused on the analysis of the risk to L-ASP hypersensitivity, finding the most remarkable results with 15 polymorphisms located at GRIA1, HLA-DRB1, NFATC2 and ASNS (Table 1) [34,[41][42][43][44]49].…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene

Lopez-Santillan

Iparraguirre

Martín-Guerrero

et al. 2017

Drug Metabolism and Personalized Therapy

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Acute lymphoblastic leukemia (ALL) is a major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients who experience severe adverse events. L-Asparaginase is an effective antineoplastic agent used in chemotherapy of ALL. Despite its indisputable indication, hypersensitivity reactions are common. In those cases, discontinuation of treatment is usually needed and anti-asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect. Till now, six pharmacogenetic studies have been performed in order to elucidate possible genetic predisposition for inter-individual differences in asparaginase hypersensitivity. In this review we have summarized the results of those studies which describe the involvement of four different genes, being polymorphisms in the glutamate receptor, ionotropic, AMPA 1 (GRIA1) the most frequently associated with asparaginase hypersensitivity. We also point to new approaches focusing on epigenetics that could be interesting for consideration in the near future.

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“…Apesar da relativa baixa toxicidade da L-asparaginase, quando comparada a outros agentes antineoplásicos (BOREK et al, 2014), devido à origem bacteriana da enzima (MEHTA et al, 2014), entre 30 e 75% dos pacientes tratados com L-asparaginase de E. coli apresentam hipersensibilidade e cerca de 70% desenvolvem anticorpos anti-L-asparaginase (FERNANDEZ et al, 2014).…”

Section: Hipersensibilidade E Formação De Anticorpos Anti-l-asparaginaseunclassified

“…e., nos regimes intermitentes e nos regimes de pós-indução, sejam eles de intensificação ou reindução (FERNANDEZ et al, 2014;PIETERS et al, 2011;CHEN et al, 2010 (FERNANDEZ et al, 2014).…”

Section: Hipersensibilidade E Formação De Anticorpos Anti-l-asparaginaseunclassified

“…A incidência de hipersensibilidade à L-asparaginase é mais comum após o centésimo dia de tratamento, e a frequência desta reação está associada à preparação farmacêutica da enzima, ao esquema de tratamento -número e frequência de injeções -à administração conjunta de outros agentes quimioterápicos, ao imunofenótipo do tumor e a fatores genéticos do paciente (FERNANDEZ et al, 2014;CHEN et al, 2010). Geralmente as primeiras reações de hipersensibilidade são contra a EcA II, levando a substituição desta pela ErA; contudo, alguns pacientes são alérgicos às duas enzimas (CHEN et al, 2010).…”

Section: Hipersensibilidade E Formação De Anticorpos Anti-l-asparaginaseunclassified

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Avaliação da atividade e resistência à clivagem proteolítica de L-asparaginases recombinantes obtidas por reação em cadeia da polimerase propensa a erro

Rodrigues¹

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HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies

Abstract: Key Points HLA-DRB1*07:01 is associated with asparaginase hypersensitivity and anti-asparaginase antibodies. HLA-DRB1 alleles that confer high-affinity binding to asparaginase epitopes lead to a higher frequency of hypersensitivity.

Cited by 94 publications

References 77 publications

HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study

HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study

Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene

Avaliação da atividade e resistência à clivagem proteolítica de L-asparaginases recombinantes obtidas por reação em cadeia da polimerase propensa a erro

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