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Japanese Journal of Ophthalmology

, Volume 62, Issue 5, pp 568–575 | Cite as

Frequencies of human leukocyte antigen alleles and haplotypes among Japanese patients with age-related macular degeneration

  • Seiji TakagiEmail author
  • Michiko Mandai
  • Yasuhiko Hirami
  • Sunao Sugita
  • Masayo Takahashi
  • Yasuo Kurimoto
Clinical Investigation

Abstract

Purpose

Stem cell therapy is a potential treatment for retinal disorders. We are currently exploring treating HLA matched patients of age-related macular degeneration (AMD) by using allogenic retinal pigment epithelium cells derived from induced pluripotent stem cells (iPS-RPE) from human leukocyte antigen (HLA) homozygote donors. The purpose of this study was to investigate the frequency of HLA class I and II alleles and haplotypes in Japanese patients with AMD.

Study design

Cross-sectional observation clinical study.

Methods

A total of 138 consecutive patients diagnosed with neovascular AMD (mean age, 76.0 ± 7.8 years, 105 men) and 300 controls were included in the study. The frequencies of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined using illumina MiSeq platform. Frequencies of HLA alleles at six loci in patients with AMD were compared with those of the controls.

Results

The alleles with the highest prevalence at each locus were A*24:02 (29.7%), B*52:01 (15.5%), C*12:02 (16.1%), DRB1*09:01 (19.1%), DQB1*06:01 (23.2%), and DPB1* 05:01 (40.5%). There were no significant associations between the HLA alleles and AMD. The most common haplotype was A*24:02-B*52:01-C*12:02-DRB1*15:02-DQB1*06:01-DPB1*09:01, with a 9.8% genetic frequency among all haplotypes, detected in 18.8% of the patients.

Conclusion

The genotype of HLA in patients with AMD was not different from that in the Japanese control population. Thus, therapy with iPS-RPEof the most frequent HLA haplotype could be a feasible alternative for AMD in a wider population.

Keywords

Age-related macular degeneration Haplotype frequency Human leukocyte antigen Japan Induced pluripotent stem cells 

Notes

Acknowledgements

This work was supported by the HLA Foundation laboratory. Although this study did not receive specific funding, we received normal data from the HLA Foundation laboratory. We thank them for their help in providing the data. We thank Dr Noriko Miyamoto and Dr Akihiro Nishida for their help in acquisition of informed consent. We also thank for professor. Goji Tomita for helpful advice. This paper received editorial support from Editage.

Conflicts of interest

S. Takagi, Grant (Alcon, AMO, HOYA, Senju), Lecture fee (Alcon); M. Mandai, Grant (Sumitomo Dainippon Pharma, Tomey), Consultant fees (Alcon, Bayer, Healios, Otsuka, Santen, Senju); Y. Hirami, Grant (Alcon, AMO, HOYA, Senju), Lecture fees (Alcon, Bayer, Santen); S. Sugita, None; M. Takahashi, Grant (Healios, Hitachi, Nichirei Biosciences, Nitta Biolab, Sagawa, Sanplatec, Santen, Shibuya, Sumitomo Dainippon Pharma, Tomey), Consultant fees (Alcon, Astellas, DAI-DAN, Eisai, Healios, Novaris, Sysmex, Takeda, Topcon, Toray); Y. Kurimoto, Grant (Alcon, HOYA, Santen, Senju), Consultant fees (Alcon, AMO, Bayer, Cannon, Kowa, Otsuka, Pfizer, Santen, Senju).

References

  1. 1.
    Fine SL, Berger JW, Maguire MG, Ho AC. Age-related macular degeneration. N Engl J Med. 2000;342(7):483–92.CrossRefPubMedGoogle Scholar
  2. 2.
    Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: 2-year results of the ANCHOR study. Ophthalmology. 2009;116(57–65):e5.Google Scholar
  3. 3.
    Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results. Ophthalmology. 2012;119:1388–98.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zarbin MA, Rosenfeld PJ. Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives. Retina. 2010;30:1350–67.CrossRefPubMedGoogle Scholar
  5. 5.
    Algvere PV, Berglin L, Gouras P, Sheng Y. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol. 1994;232:707–16.CrossRefPubMedGoogle Scholar
  6. 6.
    van Zeeburg EJ, Maaijwee KJ, Missotten TO, Heimann H, van Meurs JC. A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years. Am J Ophthalmol. 2012;153(120–7):e2.Google Scholar
  7. 7.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, et al. In vitro and In vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Investig Opthalmol Vis Sci. 2004;45:1020.CrossRefGoogle Scholar
  9. 9.
    Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379:713–20.CrossRefPubMedGoogle Scholar
  10. 10.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.CrossRefPubMedGoogle Scholar
  11. 11.
    Mandai M, Watanabe A, Kurimoto Y, Hirami Y, Morinaga C, Daimon T, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;376:1038–46.CrossRefPubMedGoogle Scholar
  12. 12.
    Taylor CJ, Bolton EM, Bradley JA. Immunological considerations for embryonic and induced pluripotent stem cell banking. Philos Trans R Soc Lond B Biol Sci. 2011;366:2312–22.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Horan J, Wang T, Haagenson M, Spellman SR, Dehn J, Eapen M, et al. Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders. Blood. 2012;120:2918–24.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Craig J, Wekerle T, Segev D, LEchler R, Oberbauer R. The tragedies for long term preservation of kidney graft function. Lancet. 2017;3(5):e15216.Google Scholar
  16. 16.
    Saito S, Ota S, Yamada E, Inoko H, Ota M. Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population. Tissue Antigens. 2000;56:522–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Ikeda N, Kojima H, Nishikawa M, Hayashi K, Futagami T, Tsujino T, et al. Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study. Tissue Antigens. 2015;85:252–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tokunaga K, Ishikawa Y, Ogawa A, Wang H, Mitsunaga S, Moriyama S, et al. Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes. Immunogenetics. 1997;46:199–205.CrossRefPubMedGoogle Scholar
  19. 19.
    Sugita S, Iwasaki Y, Makabe K, Kamao H, Mandai M, Shiina T, et al. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-matched models. Stem Cell Rep. 2016;7:635–48.CrossRefGoogle Scholar
  20. 20.
    Sugita S, Iwasaki Y, Makabe K, Kimura T, Futagami T, Suegami S, et al. Lack of T cell response to iPSC-derived retinal pigment epithelial cells from HLA homozygous donors. Stem Cell Rep. 2016;7:619–34.CrossRefGoogle Scholar
  21. 21.
    Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8:409–12.CrossRefPubMedGoogle Scholar
  22. 22.
    Thorsby E, Lie BA. HLA associated genetic predisposition to autoimmune diseases: genes involved and possible mechanisms. Transpl Immunol. 2005;14:175–82.CrossRefPubMedGoogle Scholar
  23. 23.
    Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res. 2001;20:705–32.CrossRefPubMedGoogle Scholar
  24. 24.
    Penfold PL, Liew SC, Madigan MC, Provis JM. Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration. Invest Ophthalmol Vis Sci. 1997;38:2125–33.PubMedGoogle Scholar
  25. 25.
    Goverdhan SV, Howell MW, Mullins RF, Osmond C, Hodgkins PR, Self J, et al. Association of HLA class I and class II polymorphisms with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2005;46:1726–34.CrossRefPubMedGoogle Scholar
  26. 26.
    Goverdhan SV, Khakoo SI, Gaston H, Chen X, Lotery AJ. Age-related macular degeneration is associated with the HLA-Cw*0701 Genotype and the natural killer cell receptor AA haplotype. Invest Ophthalmol Vis Sci. 2008;49:5077–82.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Enrique V, Becerril RGF, Luis P. Torres, Manuel, José M Gallardo G. HLA B27 as predisposition factor to suffer age related macular degeneration. Cell Mol Immunol. 2009;6(4):303–7.CrossRefGoogle Scholar
  28. 28.
    Cao K, Hollenbach J, Shi X, Shi W, Chopek M, Fernandez-Vina MA. Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations. Hum Immunol. 2001;62:1009–30.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyKobe City Eye HospitalKobeJapan
  2. 2.Department of OphthalmologyKobe City Medical Center General HospitalKobeJapan
  3. 3.Department of OphthalmologyToho University Ohashi Medical CenterTokyoJapan
  4. 4.Laboratory for Retinal RegenerationRIKEN Center for Developmental BiologyKobeJapan

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