ArticleInvestigative ophthalmology & visual science2021
ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A large meta-analysis identifies genes associated with anterior uveitis.Nature communications · 2023Pooled it
- Exploring the Involvement ofLife (Basel, Switzerland) · 2026Review
- Pigment loss and pseudo-albinism in Birdshot chorioretinitis.Eye (London, England) · 2026Observational
- HLA-B*51 Beyond Behcet's Disease: Topography of Symptoms, Associated Diagnoses, and Characterization of Chronic Inflammatory Arthritis Phenotypes.International journal of molecular sciences · 2026Article
- The Impact of ERAP1 and ERAP2 Haplotype Combinations on Susceptibility and Severity of Birdshot Chorioretinitis.Investigative ophthalmology & visual science · 2026Article
- The important roles of ERAP1, ERAP2 genes polymorphisms and their DNA methylation levels in pulmonary tuberculosis.BMC infectious diseases · 2025Article
- The Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis.Investigative ophthalmology & visual science · 2024Article
- HLA-A29 Negative Birdshot-like Chorioretinopathy Associated with Vitiligo-Case Report.Journal of clinical medicine · 2024Article
- Single-cell profiling identifies a CD8Nature communications · 2024Article
- A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.Cell genomics · 2024Article
- Long-Term Outcomes of Birdshot Chorioretinopathy Treated with Corticosteroids: A Case Reports.Journal of clinical medicine · 2023Article
- EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.Annals of the rheumatic diseases · 2023Review
- Some practical issues about HLA-A29 in birdshot retinochoroiditis.Journal of ophthalmic inflammation and infection · 2023Article
- Birdshot Chorioretinopathy: A Review.Journal of clinical medicine · 2022Review
- The emerging multifunctional roles of ERAP1, ERAP2 and IRAP between antigen processing and renin-angiotensin system modulation.Frontiers in immunology · 2022Review
- EnRAPtured: Is Endoplasmic Reticulum Aminopeptidase a New Clue to the Pathogenesis and ThERAPy of Uveitis?Ophthalmology science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Birdshot chorioretinopathy (BSCR) is strongly associated with HLA-A29. This study was designed to elucidate the genetic modifiers of BSCR in HLA-A29 carriers. Methods: We sequenced the largest BSCR cohort to date, including 286 cases and 108 HLA-A29-positive controls to determine genome-wide common and rare variant associations. We further typed the HLA alleles of cases and 45,386 HLA-A29 controls of European ancestry to identify HLA alleles that associate with BSCR risk. Results: Carrying a second allele that belongs to the HLA-Aw19 broad antigen family (including HLA-A29, -A30, -A31, and -A33) increases the risk for BSCR (odds ratio [OR] = 4.44; P = 2.2e-03). This result was validated by comparing allele frequencies to large HLA-A29-controlled cohorts (n = 45,386; OR > 2.5; P < 1.3e-06). We also confirm that ERAP1 and ERAP2 haplotypes modulate disease risk. A meta-analysis with an independent dataset confirmed that ERAP1 and ERAP2 haplotypes modulate the risk for disease at a genome-wide significant level: ERAP1-rs27432 (OR = 2.46; 95% confidence interval [CI], 1.85-3.26; P = 4.07e-10), an expression quantitative trait locus (eQTL) decreasing ERAP1 expression; and ERAP2-rs10044354 (OR = 1.95; 95% CI, 1.55-2.44; P = 6.2e-09), an eQTL increasing ERAP2 expression. Furthermore, ERAP2-rs2248374 that disrupts ERAP2 expression is protective (OR = 0.56; 95% CI, 0.45-0.70; P = 2.39e-07). BSCR risk is additively increased when combining ERAP1/ERAP2 risk genotypes with two copies of HLA-Aw19 alleles (OR = 13.53; 95% CI, 3.79-54.77; P = 1.17e-05). Conclusions: The genetic factors increasing BSCR risk demonstrate a pattern of increased processing, as well as increased presentation of ERAP2-specific peptides. This suggests a mechanism in which exceeding a peptide presentation threshold activates the immune response in choroids of A29 carriers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.