Influence of molecular genetics in Vogt-Koyanagi-Harada disease

Abstract

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder against melanocytes. Recent studies have identified multiple genetic factors that might be associated with the pathogenesis of VKH disease. We performed an electronic database search of PubMed, MEDLINE, and EMBASE, and all relevant papers published up to 13 June 2014 were reviewed. A total of 1,031 publications including articles relevant to the genetics of VKH disease and the references of these articles were reviewed. The review identified a number of genetic factors which might be involved in the pathogenesis of VKH disease, some of which may alter the clinical course of VKH disease. Genes which might be involved in the pathogenesis of VKH disease included genes expressing HLA, complement factor H, interleukins, cytotoxic T-lymphocyte antigen 4 (CTLA-4), killer cell immunoglobulin-like receptors (KIR), programmed cell death 1 (PDCD1), protein tyrosine phosphatase non-receptor 22 (PTPN22), osteopontin, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), macrophage migration inhibitory factor (MIF), and other immune response genes. Further studies to explore the correlation among different genotypes and phenotypes of VKH disease will be useful to shed light on the pathogenesis of uveitis in VKH disease and may facilitate the development of new treatment modalities of uveitis in VKH disease.

Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes

“…Besides HLA-DR involvement in VKHD, recently accumulating evidence has demonstrated association of non-HLA genetic factors in VKHD, i.g. cytotoxic T-lymphocyte antigen 4 gene, interleukin genes, macrophage migration inhibitory factor gene and osteopontin gene [ 37 ]. More recently, on genome wide analysis, three loci were associated with VKHD susceptibility IL23R-C1orf141, rs117633859; ADO-ZNF365-EGR2, rs442309 and HLA-DRB1/DQA1, rs3021304 [ 38 ].…”

Correlation between visual acuity and human leukocyte antigen (HLA)-DRB1*04 in patients with Vogt-Koyanagi-Harada disease

“…VKH disease was diagnosed according to the criteria of Sugiura [11] and the VKH Disease Committee [12]. None of the patients had any medical or ocular history at the In HLA typing by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP), typing specificity is part of the amplification step [9].…”

Clinical diagnosis and treatment recommendations for ocular toxicities of targeted therapy and immune checkpoint inhibitor therapy

“…The autoimmune reaction against melanocytes in VKH is mainly mediated by T lymphocytes, and the antitumor effects of immune checkpoint inhibitors are also achieved by enhancing T cell function, suggesting that they might be the same T cell clone . Interestingly, CTLA4 and PD‐1 genetic polymorphisms have been found among VKH patients . CTLA4 and PD‐1 antibodies may disrupt the balance of tumor cell killing and immune tolerance to melanocytes via CTLA4 or PD‐1 signals and therefore be involved in the pathogenesis of VKH.…”

“…21 Interestingly, CTLA4 and PD-1 genetic polymorphisms have been found among VKH patients. 22 CTLA4 and PD-1 antibodies may disrupt the balance of tumor cell killing and immune tolerance to melanocytes via CTLA4 or PD-1 signals and therefore be involved in the pathogenesis of VKH.…”