The present study revealed a correlation between HLA04 allele type and visual outcomes before and after initiating systemic corticosteroid therapy in treatment-naïve patients with VKH disease.
Previous studies have reported that HLAs are cell surface molecules mediating interactions with leukocytes. Therefore, HLA plays an important role in immune system function as well as in the pathogenesis of autoimmune diseases, including VKH. Almost 40 years ago, an association of HLA-BW22J and VKH was reported . More articles have since been published on the association of different types of HLA and VKH. Among these, the HLA-DR4 serotype and its corresponding allele HLA-DRB1*04 have mostly been investigated . A meta-analysis by Shi et al. confirmed the association between VKH and HLA-DR4/DRB1*04, and found the strength of association differed between different ethnic groups, and identified HLA-DRB1* 0404, 0405 and 0410 as risk sub-alleles, and 0401 as a protective sub-allele [11,12].
In this study, a significance result was found from linear regression among the three groups of homozygotes, heterozygotes, and normal subjects in logMAR BCVA at baseline.
For groups not having HLA-DR4/DRB1*04, the diagnosis may be not typical for VKH. However, both homozygous and heterozygous groups were above the regression line, which was considered to have a certain statistical meaning.
In a study of type 1 diabetes in Japanese, disease susceptibility differed between homozygotes and heterozygotes . A similar situation may also apply to VKH patients. Even before and after steroid treatment, homozygotes showed the best post-treatment visual acuity. Normal subjects (no HLA-DRB1*04 allele) had the poorest visual acuity after treatment. This indicates that therapeutic response and sensitivity to steroid treatment may depend on allele HLA-DRB1*04. Understanding the pathogenesis underlying these results is difficult. However, previous reports such as haplotype linkage disequilibrium studies have suggested associations with genes closely related to immunity and inflammation, such as IKBL gene and TNFA gene present in HLA class III [14,15,16]. Allele HLA-DRB1*04 is a disease-associated gene frequently found in VKH, but this study considered the possibility of disease resistance. On the other hand, another report showed the presence of the HLA-DRB1*04 allele is related to the prolongation of VKH in previous research in Japanese patients . We know that allele HLA-DRB1*04 is the key to VKH, but the details remain unclear. According to a previous report, CCT correlates with the vision prognosis in VKH . However, the small number of cases was problematic in this case series, and the correlation between allele HLA-DRB1*04 and CCT was not determined.
In the future, the complete genetic predisposition of VKH is expected to be elucidated, leading to the development of new treatments and preventions.
We acknowledge these potential issues as well as the need for future worldwide studies into the correlations between allele HLA-DRB1*04 and visual outcomes and rulein VKH.