Targeting ERAP in autoimmune uveitis

Birdshot Uveitis (BU) is a rare form of uveitis posterior, with 200-250 patients in The Netherlands. Interestingly, there is a 100% association with one Human Leukocyte Antigen (HLA), HLA-A29:02. However, 7-10% of the European Caucasian population carries at least one HLA-A29:02 allele. Therefore a more complex disease mechanism is involved. A recent study by Kuiper et al. (2018) showed a strong association with ERAP genes in BU patients. In particular a selection of SNPs are involved in protein activity of two endoplasmic reticulum aminopeptidases (ERAPs). These ERAPs trim peptides in smaller fragments, followed by presentation of these peptides via HLA.

The main goal of my research is getting a better understanding of the role of ERAPs in BU. The interplay between specific (eye)antigens, the influence of ERAPs and antigen presentation via HLA-A29:02 is still unclear. In addition, ERAPs are not only described to influence disease progression in BU patients, but also in other (auto-immune) diseases ERAP hypo-/hyperactivity is involved (Behçet's disease, ankylosing spondylitis). Since BU is the only 100% associated HLA related disease, the involvement of ERAPs on peptides processing may explain the auto-immune like inflammation found in BU patients. Furthermore, the role of ERAPs in BU could be translated to other ERAP- and HLA-associated diseases.

Wouter Venema