SynthesisHuman molecular genetics2018
Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis.
Synthesis in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Exploring the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis.Rheumatology (Oxford, England) · 2026Pooled it
- A large meta-analysis identifies genes associated with anterior uveitis.Nature communications · 2023Pooled it
- Review
- Exploring the Involvement ofLife (Basel, Switzerland) · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- The Impact of ERAP1 and ERAP2 Haplotype Combinations on Susceptibility and Severity of Birdshot Chorioretinitis.Investigative ophthalmology & visual science · 2026Article
- The potential applications of peptide-loading complex in cancer treatment.Frontiers in immunology · 2025Review
- Single-cell profiling identifies a CD8Nature communications · 2024Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- Biology of HLA class I associated inflammatory diseases.Best practice & research. Clinical rheumatology · 2024Review
- Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review.Diagnostics (Basel, Switzerland) · 2024Review
- A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.Cell genomics · 2024Article
- Association ofFrontiers in immunology · 2024Article
- Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).Genes and immunity · 2023Review
- Review
- EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.Annals of the rheumatic diseases · 2023Review
- Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis.eLife · 2023Article
- Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease.American journal of human genetics · 2023Article
- Some practical issues about HLA-A29 in birdshot retinochoroiditis.Journal of ophthalmic inflammation and infection · 2023Article
- Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.Gastroenterology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed 'MHC-I (major histocompatibility complex class I)-opathy' family. Genetic studies have pinpointed the endoplasmic reticulum aminopeptidase (ERAP1) and (ERAP2) genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression. We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC-I-opathies. We show that the risk ERAP1 haplotype conferred significantly altered expression of ERAP1 isoforms in transcriptomic data (n = 360), resulting in lowered protein expression and distinct enzymatic activity. Both the association for rs10044354 (meta-analysis: odds ratio (OR) [95% CI]=2.07[1.58-2.71], P = 1.24 × 10(-7)) and rs2287987 (OR[95% CI]: =2.01[1.51-2.67], P = 1.41 × 10(-6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either variant alone [meta-analysis: P=3.9 × 10(-9)]. Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n = 3353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly.
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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.