Genetics of Birdshot Chorioretinopathy

Abstract

Birdshot chorioretinopathy is a bilateral, posterior uveitis that affects primarily Caucasians. Although the genetic basis of disease is not completely understood, certain factors are known, such as the strong association with human leukocyte antigen (HLA)-A29. However, given the prevalence of the HLA-A29 allele in the general population, if it were the only factor required for disease, many more people would have birdshot chorioretinopathy. It has been suggested that some environmental factor may trigger this disease entity in those who are genetically predisposed based on inheritance of the HLA-A29 allele.

A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy

“…To date, the association of HLA-A29 with BSCR is the strongest association described between an HLA class I allele and human disease (2,6). Although this association has been known for over three decades (1), lack of understanding of the contribution of HLA-A29 to the pathogenesis of BSCR, impeded it to become an absolute criterion for diagnosis (22).…”

“…BSCR manifests as a severe progressive intraocular inflammation of the posterior eye segment, typically leading to extensive retinal atrophy and blindness (4,5). The disease is most often observed in middle-aged and elderly individuals of European descent and has a slight female predominance (3,6). Current treatment strategies include various immunosuppressive medications but fail to prevent or cease the retinal atrophy.…”

“…Current treatment strategies include various immunosuppressive medications but fail to prevent or cease the retinal atrophy. HLA-A29 is relatively common in European populations, but only a tiny subset of HLA-A29-positive individuals develops BSCR (6). It is therefore assumed that other genes than HLA-A and additional exogenous factors are involved in the development of the disease.…”

HLA-A29 and Birdshot Chorioretinopathy

“…13 The role of the differential distribution of HLA-A*29:01 and HLA-A*29:02, the two main subtypes of HLA-A29, in Caucasians and other populations has been actively debated as an explanation for the selective development of the disease in patients of European descent. 14 The respective frequencies of the HLA-A*29:01 and HLA-A*29:02 allele in different populations are summarized in Table 2. It had been suggested that the HLA-A*29:02 subtype is particularly important in conferring risk for birdshot chorioretinopathy.…”

Why birdshot retinochoroiditis should rather be called ‘HLA-A29 uveitis’?

“… 10 The HLA-A29 MHC antigen is present in around 7% of Caucasian populations. 11 It is increasingly likely that the association is closer to 100% rather than >95% because false negatives were not so rare when the antibody testing method was used. 12 The rate of false-negative results could be reduced with PCR-based testing.…”