ArticleInvestigative ophthalmology & visual science2026
The Impact of ERAP1 and ERAP2 Haplotype Combinations on Susceptibility and Severity of Birdshot Chorioretinitis.
Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The MHC-I-opathy architecture: immunogenetic and biomechanical determinants of disease expression.Zeitschrift fur Rheumatologie · 2026Review
- Exploring the Involvement ofLife (Basel, Switzerland) · 2026Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To investigate how ERAP1 and ERAP2 genotype combinations influence susceptibility and severity in birdshot chorioretinitis (BSCR), an HLA-A29-associated disease with variable visual outcomes. Methods: We analyzed ERAP1 and ERAP2 haplotypes in 406 HLA-A29-positive BSCR patients and 106 HLA-A29-positive controls. ERAP1 activity was inferred from published enzymatic efficiency data and ERAP2 activity from protein expression data. Predicted peptide trimming activity was assigned to each patient. Correlation and multivariable regression analyses were performed to evaluate associations between ERAP1 and ERAP2 genotypes and disease severity, assessed by disease onset (age at first symptoms) and visual outcomes: best-corrected visual acuity, mean deviation, pattern standard deviation, and foveal threshold. Results: We observed high genetic diversity, with 86 distinct ERAP1-ERAP2 genotype combinations among BSCR patients. The Hap10-Hap8 ERAP1 pairing was most frequent in BSCR (13.6%) and less common in controls (6.6%). The ERAP2 HapA-HapA genotype was more frequent in patients (33.7%) than in controls (19.8%). The mean estimated total peptide trimming activity of ERAP1 per individual was significantly lower in BSCR patients than in controls (adjusted P = 6.2e-07), whereas ERAP2 activity was higher (adjusted P = 0.0025). No robust associations between ERAP1 or ERAP2 activity and visual outcomes were detected. In multivariable models, visual outcomes were predominantly driven by age and disease duration. Conclusions: Our findings support a model in which ERAP1 and ERAP2 contribute to BSCR susceptibility, but have limited influence on disease severity. The observed pattern of reduced ERAP1 and elevated ERAP2 activity in BSCR patients may affect peptide processing and HLA-A29-mediated presentation.
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