Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Japanese Journal of Ophthalmology
Published in: Japanese Journal of Ophthalmology 5/2018

01-09-2018 | Clinical Investigation

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

Published in: Japanese Journal of Ophthalmology | Issue 5/2018

Login to get access

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.
Literature
1.
Fine SL, Berger JW, Maguire MG, Ho AC. Age-related macular degeneration. N Engl J Med. 2000;342(7):483–92.CrossRefPubMed
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.
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRef
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.CrossRef
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.CrossRefPubMed
22.
Thorsby E, Lie BA. HLA associated genetic predisposition to autoimmune diseases: genes involved and possible mechanisms. Transpl Immunol. 2005;14:175–82.CrossRefPubMed
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.CrossRefPubMed
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.PubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRef
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.CrossRefPubMed
Metadata
Title
Frequencies of human leukocyte antigen alleles and haplotypes among Japanese patients with age-related macular degeneration
Publication date
01-09-2018
Published in
Japanese Journal of Ophthalmology / Issue 5/2018
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-018-0611-8

Other articles of this Issue 5/2018

Japanese Journal of Ophthalmology 5/2018 Go to the issue

Clinical Investigation

Visual function and inner retinal structure correlations in aquaporin-4 antibody-positive optic neuritis

Clinical Investigation

Corneal crosslinking for keratoconus in Japanese populations: one year outcomes and a comparison between conventional and accelerated procedures

Clinical Investigation

Changes in conjunctival–scleral thickness after strabismus surgery measured with anterior segment optical coherence tomography

Laboratory Investigation

Near-infrared and short-wave autofluorescence in ocular specimens

Clinical Investigation

Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia: first year results

Clinical Investigation

Comparison of subfoveal choroidal structures in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy