A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis

Summary Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life‐threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association be...

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Published in:International journal of immunogenetics 2011-08, Vol.38 (4), p.303-309
Main Authors: Cristallo, A. F., Schroeder, J., Citterio, A., Santori, G., Ferrioli, G. M., Rossi, U., Bertani, G., Cassano, S., Gottardi, P., Ceschini, N., Barocci, F., Ribizzi, G., Cutrupi, V., Cairoli, R., Rapisarda, V., Pastorello, E. A., Barocci, S.
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
allopurinol
Bone marrow
Carbamazepine
Case-Control Studies
DQA1 protein
Drb1 protein
Drugs
Female
Gene Frequency - genetics
Genetic markers
Genotyping
Haplotypes
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class II - genetics
Humans
Italy
Major histocompatibility complex
Male
Middle Aged
paracetamol
Population genetics
Risk Factors
Side effects
Statistical analysis
Statistics
Stem cells
Stevens-Johnson syndrome
Stevens-Johnson Syndrome - genetics
Stevens-Johnson Syndrome - immunology
Toxic epidermal necrolysis
Young Adult
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Summary:Summary Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life‐threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA‐class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case–control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA‐A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA‐A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug‐induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P = 0.00002, Pc = 0.0011; 28.6% vs 0%, P = 0.00002, Pc = 0.001; 28.6% vs 0%, P = 0.00002, Pc = 0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P = 0.003; 28.6% vs 1.7%, P = 0.005; 28.6% vs 3.5%, P = 0.037, respectively), appeared no more statistically different after P correction (Pc = 0.248; Pc = 0.29; Pc = 1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol‐induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug‐induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01‐DRB1*13:02 and DRB1*15:02‐DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P = 0.00001, Pc = 0.00028; 14.2% vs 0.43%, P = 0.00001, Pc = 0.00028, respectively). Our results show that in contrast to SCAR‐related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR‐related to allopurinol even when a limited number of patients are considered.
ISSN:1744-3121
1744-313X
DOI:10.1111/j.1744-313X.2011.01011.x