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Human leucocyte antigen association of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications in Han Chinese
  1. Kevin Sheng-Kai Ma1,2,
  2. Wen Hung Chung3,4,5,6,7,8,
  3. Yi-Jen Hsueh2,
  4. Shin-Yi Chen9,
  5. Katsushi Tokunaga10,
  6. Shigeru Kinoshita11,
  7. David H K Ma2,12,13,14,
  8. Mayumi Ueta15
  1. 1Department of Life Science, National Taiwan University, Taipei, Taiwan
  2. 2Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
  3. 3Department of Dermatology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
  4. 4Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
  5. 5Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  6. 6Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan
  7. 7Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  8. 8Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  9. 9Department of Ophthalmology, Keelung Chang Gung Memorial Hospital of the CGMF, Keelung, Taiwan
  10. 10Department of Human Genetics, The University of Tokyo Graduate School of Medicine Faculty of Medicine, Bunkyo-ku, Tokyo, Japan
  11. 11Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  12. 12Department of Ophthalmology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China
  13. 13Department of Chinese Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan
  14. 14Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  15. 15Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  1. Correspondence to Dr David H K Ma, Department of Ophthalmology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan; davidhkma{at}yahoo.com; Dr Mayumi Ueta, Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; mueta{at}koto.kpu-m.ac.jp

Abstract

Background/aims Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by cold medicine (CM) may result in severe ocular complications (SOCs). The purpose of this study was to investigate the human leucocyte antigen (HLA) polymorphism pattern in CM-induced patients with SJS/TEN developing SOCs.

Methods All participants, including patients with SJS/TEN (n=33) and control patients (n=98), were enrolled through visits to the clinic from 2016 to 2017. SOCs were diagnosed (n=26) via a chart review or eye examination. Patient saliva was collected with commercialised kits and genotyped with PCR assays followed by hybridisation with sequence-specific oligonucleotide (SSO) probes (PCR-SSO) using commercial bead-based typing kits.

Results In all patients with SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was significantly higher than that in controls (OR=3.24, 95% CI=1.09 to 9.60, p=0.049), as was the genotype frequency (OR=3.89, 95% CI=1.49 to 10.16, p=0.007). In patients with CM-SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was higher than that in controls (OR=5.56, 95% CI=1.52 to 20.00, p=0.016), as was the allele frequency (OR=6.67, 95% CI=2.33 to 20.00, p=0.001). In patients with CM-SJS/TEN with SOCs, the HLA-B*46:01 allele frequency was significantly higher than that in controls (OR=3.85, 95% CI=1.52 to 10.00, p=0.008).

Conclusions The HLA-A*02:07 and HLA-B*46:01 alleles were significantly associated with SOCs among Han Chinese patients with CM-SJS/TEN. These findings demonstrate the genetic diversity in SJS pathogenesis among different ethnic groups.

  • cornea
  • conjunctiva
  • drugs
  • genetics
  • ocular surface
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Footnotes

  • Contributors KS-KM—data analysis and writing of the manuscript. WHC—providing study subjects and contributing opinion in Discussion. Y-JH—IRB application and subsequent inspection. S-YC—patient examination and recording. KT—HLA genotyping and analysis. SK—contributing opinion in Discussion. DHKM—patient collection, supervising manuscript preparation, fund provider and corresponding author. MU—study design, sample handling, fund provider and corresponding author.

  • Funding This work was supported by Chang Gung Memorial Hospital grants (CMRPG3G0021-3, CMRPG1H0091) and the Japan Society for the Promotion of Science (JSPS) Core-to-Core Program grants-in-aid Type A Advanced Research Networks.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study procedure used to collect SJS/TEN and control patient genomes for HLA analysis was approved by the Institutional Review Boards of Chang Gung Medical Foundation (IRB approval number: 104-0927B) and of Kyoto Prefectural University of Medicine. All experimental procedures were conducted in accordance with the principles set forth in the Helsinki Declaration.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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