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Seiji Takagi; Frequency of Human Leucocyte Antigen -A, C, B, DRB1, DQB1, and DPB1 Alleles and Haplotypes in Japanese Patients with Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2300.
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© ARVO (1962-2015); The Authors (2016-present)
In stem cell therapy, the human leucocyte antigen (HLA) plays an important role in graft rejection. Therefore, retinal pigment epithelium (RPE) graft cells, derived from HLA-matched induced pluripotent stem cells (iPSCs), are considered good candidates as sources for allogenic cell therapy in age related macular degeneration (AMD). Moreover, RPE cells derived from iPSCs with the highest frequencies of HLA haplotypes could be used for an even wider spectrum of patients. HLA alleles and haplotypes have been known to be unique in each ethnic group and to have significant positive and negative associations with AMD. However, the HLA alleles and haplotypes in Japanese patients with AMD remain unknown. Therefore, the present cross-sectional observational study investigates the HLA A, C, B, DRB1, DQB1, and DPB1 allele and haplotype frequencies in Japanese patients with AMD.
Eighty-four consecutive patients with neovascular AMD (76.2 ± 16.5 y, male: 40), who had active exudative lesions and were receiving anti- vascular endothelial growth factor therapy, from September 2015 to January 2016 were included in this study. We determined the frequency of HLA-A,-C,-B, DRB1,-DQB1,-DPB1 allele using next generation sequencing. The haplotype frequencies were counted directly by segregation, and the match ratio with highest haplotype frequency in the Japanese population (A*24:02, B*52:01, C*12:02, DRB1*15:02, DQB1*06:01, DPB1*09:01),previously reported, was analyzed.
We identified 14 A, 27 B, 16 C, 23 DRB1, 11 DQB1, and 11 DPB1 alleles. 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%). The match ratio with the highest haplotype frequency in the Japanese population and this study group was 9.5%.
The frequency of HLA A, C, B, DRB1, DQB1, and DPB1 alleles and haplotypes in Japanese patients with neovascular AMD is equivalent to that in normal Japanese individuals, as reported. The RPE cells therapy, which is derived from iPSCs with frequent haplotype of HLA, could be options for AMD treatment for large population.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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