P165 New relevant associations with vogt-koyanagi-disease (VKH) were found in Mexicans, using NGS technology. A new allele at DPA1 locus was detected in a VKH patient

Abstract

Aim VKH is a systemic autoimmune disorder affecting tissues containing melanin, mainly the eyes. It is characterized by severe bilateral granulomatous uveitis. VKH is a T cell mediated disease vs. specific auto-antigens relevant in its pathogenesis. We and others showed that a shared epitope in the first DRB1 domain is clearly associated with VKH. DRB1*04:05 and 04:04 are strongly involved in Mexicans and other contributing DRB1 alleles, were also published by us: DRB1*04:05> *04:04 > *04:07 > *01:01 > *01:02. We now explored the whole MHC region, to unravel the complete MHC genetics of VKH. Methods We selected 77 unrelated donors from Mexico City and 49 VKH patients from the APEC. DNA samples were extracted in the Maxwell 16 instrument. For HLA typing, the MIA FORA NGS FLEX HLA Kit (Immucor, Inc) and The Illumina MiSeq, were used. Sequence analysis was performed with the Mia Fora software. Genotypes were assigned at all loci unambiguously, except for DPB1. Allele and haplotype frequencies (AF/HF) were done with the Arlequin, PyPop and Hapl-o-Mat v.1.1 software. Results A hierarchy of Class I/class II associations were found with deep sequencing: DQB1*03:02:01 (p = 0.000007); DQA1*03:01:01(p = 0.0002); C*03:04:01 (p = 0.007); DRB1*04:04:01(p = 0.005); DRB1 *04:07:01 (p = 0.01); DRB1*04:05:01; (p = 0.02); B*48:01:01 (p = 0.04); A*68:01:01(p = 0.02); DPB1 *03:01:01(p = 0.02). The OR was between 2.9 and 7.3. Amerindian (AMI), Hispanic and Asian alleles are evident at all loci. The most frequent haplotype in VKH is of Mexican AMI descent : A*02:01:01 B*39:05:01 C*07:02:01 DRB1*04:07:01