The Journal of allergy and clinical immunology · 2026
HLA-B alleles confer susceptibility to sulfasalazine-induced severe cutaneous adverse reactions.
СтатьяМетаанализПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Chuang-Wei, Chen Wei-Ti, Chen Chun-Bing, Chu Chia-Yu, Chung-Yee Hui Rosaline, Lu Chun-Wei, Chiu Tsu-Man, Hung Shuen-Iu, Huei Huang Yu, Tassaneeyakul Wichittra, Choon Siew-Eng, Nakkam Nontaya, Sukasem Chonlaphat, Jan Wu Yeong-Jian, Chung Hsin-Yu, Lung Jr-Hau, Chang Jeng-Shou, Lee Yun-Shien, Chang Ya-Ching, Yu Kuang-Hui, Teng Yu-Chuan, Lin Shang-Hung, Lai Kuo-Chu, Hou Hsin-Han, Wu Jennifer, Chi Min-Hui, Lee Hua-En, Yu-Wei Lin Yang, Lin Yu-Jr, Chung Wen-Hung, Taiwan/Asian Severe Cutaneous Adverse Reaction Consortium
Аннотация
BACKGROUND: Sulfasalazine is a disease-modifying antirheumatic drug used to treat arthritis and ankylosing spondylitis. However, it may cause life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms.
OBJECTIVE: Genetic predisposition to sulfasalazine-induced SCARs was assessed.
METHODS: This multicountry genetic study involved discovery, replication, and meta-analysis cohorts. The discovery cohort comprised 62 cases of sulfasalazine-induced SCARs and 75 sulfasalazine-tolerant subjects as well as 657 population controls from China and Taiwan who underwent whole-exome sequencing. The replication cohort comprised additional 17 cases and 2038 population controls from Taiwan who underwent HLA genotyping. The meta-analysis cohort comprised a total of 105 cases from Japan, Thailand, Malaysia, Taiwan, and China, together with 23,743 country-matched population controls. Functional immune mechanisms were explored with ex vivo lymphocyte activation assays.
RESULTS: In the discovery cohort, rs9266217 in HLA-B exhibited the strongest association. HLA genotyping in replication cohort and phenotype stratification found 4 HLA-B alleles that jointly yielded 84.8% sensitivity (P = 2.3 × 10-24) in predicting sulfasalazine-induced SCARs in the Chinese population. Meta-analysis across 4 Asian countries confirmed significant associations for 3 alleles. Functional assays showed that sulfasalazine or its active metabolite, sulfapyridine, markedly increased granulysin release from CD8+ T cells of affected patients, supporting an HLA-restricted reaction.
CONCLUSION: Multiple HLA-B alleles (B∗39:01, B∗13:01, and B∗38:02) are strongly associated with sulfasalazine-induced SCARs in Asians.
OBJECTIVE: Genetic predisposition to sulfasalazine-induced SCARs was assessed.
METHODS: This multicountry genetic study involved discovery, replication, and meta-analysis cohorts. The discovery cohort comprised 62 cases of sulfasalazine-induced SCARs and 75 sulfasalazine-tolerant subjects as well as 657 population controls from China and Taiwan who underwent whole-exome sequencing. The replication cohort comprised additional 17 cases and 2038 population controls from Taiwan who underwent HLA genotyping. The meta-analysis cohort comprised a total of 105 cases from Japan, Thailand, Malaysia, Taiwan, and China, together with 23,743 country-matched population controls. Functional immune mechanisms were explored with ex vivo lymphocyte activation assays.
RESULTS: In the discovery cohort, rs9266217 in HLA-B exhibited the strongest association. HLA genotyping in replication cohort and phenotype stratification found 4 HLA-B alleles that jointly yielded 84.8% sensitivity (P = 2.3 × 10-24) in predicting sulfasalazine-induced SCARs in the Chinese population. Meta-analysis across 4 Asian countries confirmed significant associations for 3 alleles. Functional assays showed that sulfasalazine or its active metabolite, sulfapyridine, markedly increased granulysin release from CD8+ T cells of affected patients, supporting an HLA-restricted reaction.
CONCLUSION: Multiple HLA-B alleles (B∗39:01, B∗13:01, and B∗38:02) are strongly associated with sulfasalazine-induced SCARs in Asians.