HLA-B alleles confer susceptibility to sulfasalazine-induced severe cutaneous adverse reactions
8
Issued Date
2026-01-01
Resource Type
ISSN
00916749
eISSN
10976825
Scopus ID
2-s2.0-105041035951
Pubmed ID
42092593
Journal Title
Journal of Allergy and Clinical Immunology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Allergy and Clinical Immunology (2026)
Suggested Citation
Wang C.W., Chen W.T., Chen C.B., Chu C.Y., Chung-Yee Hui R., Lu C.W., Chiu T.M., Hung S.I., Huei H.Y., Tassaneeyakul W., Choon S.E., Nakkam N., Sukasem C., Jan Wu Y.J., Chung H.Y., Lung J.H., Chang J.S., Lee Y.S., Chang Y.C., Yu K.H., Teng Y.C., Lin S.H., Lai K.C., Hou H.H., Wu J., Chi M.H., Lee H.E., Yu-Wei Lin Y., Lin Y.J., Chung W.H. HLA-B alleles confer susceptibility to sulfasalazine-induced severe cutaneous adverse reactions. Journal of Allergy and Clinical Immunology (2026). doi:10.1016/j.jaci.2026.04.017 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117287
Title
HLA-B alleles confer susceptibility to sulfasalazine-induced severe cutaneous adverse reactions
Author(s)
Wang C.W.
Chen W.T.
Chen C.B.
Chu C.Y.
Chung-Yee Hui R.
Lu C.W.
Chiu T.M.
Hung S.I.
Huei H.Y.
Tassaneeyakul W.
Choon S.E.
Nakkam N.
Sukasem C.
Jan Wu Y.J.
Chung H.Y.
Lung J.H.
Chang J.S.
Lee Y.S.
Chang Y.C.
Yu K.H.
Teng Y.C.
Lin S.H.
Lai K.C.
Hou H.H.
Wu J.
Chi M.H.
Lee H.E.
Yu-Wei Lin Y.
Lin Y.J.
Chung W.H.
Chen W.T.
Chen C.B.
Chu C.Y.
Chung-Yee Hui R.
Lu C.W.
Chiu T.M.
Hung S.I.
Huei H.Y.
Tassaneeyakul W.
Choon S.E.
Nakkam N.
Sukasem C.
Jan Wu Y.J.
Chung H.Y.
Lung J.H.
Chang J.S.
Lee Y.S.
Chang Y.C.
Yu K.H.
Teng Y.C.
Lin S.H.
Lai K.C.
Hou H.H.
Wu J.
Chi M.H.
Lee H.E.
Yu-Wei Lin Y.
Lin Y.J.
Chung W.H.
Author's Affiliation
Tsinghua University
National Tsing Hua University
Chang Gung Memorial Hospital
National Yang-Ming University Taiwan
Chang Gung University
National Taiwan University College of Medicine
Chang Gung University College of Medicine
Ruijin Hospital
Monash University Malaysia
Chung Shan Medical University Hospital
Ramathibodi Hospital
Faculty of Medicine, Khon Kaen University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Ming Chuan University
Xiamen Chang Gung Hospital
The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) research group
National Tsing Hua University
Chang Gung Memorial Hospital
National Yang-Ming University Taiwan
Chang Gung University
National Taiwan University College of Medicine
Chang Gung University College of Medicine
Ruijin Hospital
Monash University Malaysia
Chung Shan Medical University Hospital
Ramathibodi Hospital
Faculty of Medicine, Khon Kaen University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Ming Chuan University
Xiamen Chang Gung Hospital
The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) research group
Corresponding Author(s)
Other Contributor(s)
Abstract
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.