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  • Human leucocyte antigen alleles confer susceptibility and progression to Graves’ ophthalmopathy in a Southern Chinese population

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Laboratory science
Human leucocyte antigen alleles confer susceptibility and progression to Graves’ ophthalmopathy in a Southern Chinese population
  1. Xiaosheng Huang1,2,
  2. Guiqin Liu1,2,
  3. Shaoyi Mei1,2,
  4. Jiamin Cai2,
  5. Jing Rao1,
  6. Minzhong Tang3,
  7. Tianhui Zhu1,2,
  8. Wenchiew Chen1,
  9. Shiming Peng1,2,
  10. Yan Wang1,
  11. Ye Ye2,
  12. Tong Zhang1,
  13. Zhihui Deng4,5,
  14. Jun Zhao1,2
  1. 1 Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated to Jinan University, Shenzhen, Guangdong, China
  2. 2 School of Ophthalmology & Optometry, Shenzhen University, Shenzhen, Guangdong, China
  3. 3 Cancer Center, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
  4. 4 Immunogenetics Laboratory, Shenzhen Blood Center, Shenzhen, Guangdong, China
  5. 5 Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
  1. Correspondence to Zhihui Deng, Immunogenetics Laboratory, Shenzhen Blood Center, Shenzhen, China, and Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; zhihui_deng{at}aliyun.com
  2. Jun Zhao, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated to Jinan University and School of Ophthalmology & Optometry Affiliated to Shenzhen University, Shenzen, China; doctorzhaojun{at}163.com

Abstract

Purpose To evaluate the contributions of human leucocyte antigen (HLA) class I and II genes in the development of Graves’ ophthalmopathy (GO) in a Southern Chinese population.

Methods Eight HLA loci were genotyped and analysed in 272 unrelated patients with Graves’ disease (GD) or the proptosis and myogenic phenotypes of GO, and 411 ethnically matched control subjects.

Results The allele frequencies of HLA-DRB1*16:02 and -DQB1*05:02 in the GD, proptosis and myogenic groups, HLA-B*38:02 and -DQA1*01:02 in the myogenic group were significantly higher than those in the control group, respectively (all corrected p values <0.05, OR >2.5). The haplotype frequencies of HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02 and HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01 in the proptosis and myogenic groups, and HLA-A*02:03-B*38:02-C*07:02 and HLA-A*02:03-B*38:02-C*07:02-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01 in the myogenic group were significantly higher than those in the control group respectively (all corrected p values <0.05, OR >2.5). The potential epitopes (‘FLGIFNTGL’ of TSHR, ‘IRHSHALVS’, ‘ILYIRTNAS’ and ‘FVFARTMPA’ of IGF-1R) were fitted exactly in the peptide-binding groove between HLA-DRA1-DRB1*16:02 heterodimer, and the epitopes (‘ILEITDNPY’ of THSR, ‘NYALVIFEM’ and ‘NYSFYVLDN’ of IGF-1R) were also fitted exactly in the peptide-binding groove between HLA-DQA1*01:02-DQB1*05:02 heterodimer.

Conclusions The HLA-DRB1*16:02 and -DQB1*01:02 alleles might be risk factors for GD including the proptosis and myogenic phenotypes of GO. The alleles HLA-B*38:02, -DQA1*01:02, the HLA haplotypes consisting of HLA-B*38:02, -DRB1*16:02, -DQA1*01:02 and -DQB1*05:02 might be susceptibility risk factors for GO. Simultaneously, some epitopes of TSHR and IGF-1R tightly binding to groove of HLA-DRA1-DRB1*16:02 or HLA-DQA1*01:02-DQB1*05:02 heterodimers might provide some hints on presenting the pathological antigen in GO.

  • Genetics
  • Immunology
  • Orbit
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bjophthalmol-2020-317091

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    Footnotes

    • XH and GL contributed equally

    • ZD and JZ contributed equally

    • Contributors XH and GL contributed equally to this work. ZD and JZ contributed equally to this work. XH, JZ and ZD contributed to study design, data analysis, result interpretation and manuscript drafting. GL contributed to provide the information and blood samples of participates. XH, SM, JC, JR, TZ, WC, SP, YW and YY contributed to data acquisition and management. XH, MT, TZ and JZ contributed to data analysis. All authors contributed to manuscript drafting and its critical revision for final content.

    • Funding This study was supported by Science, Technology and Innovation Commission of Shenzhen Municipality under Grant (number GJHZ20180420180937076, number JCYJ20180228164400218 and number JCYJ20190806152001762), Sanming Project of Medicine in Shenzhen Grant (number SZSM201812090), and Shenzhen Key Medical Discipline Construction Fund (number SZXK070).

    • Competing interests None declared.

    • Patient consent for publication Not require.

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

    • Data availabilty statement Data are available upon reasonable request.

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