ArticleAnnals of the rheumatic diseases2016
Silencing or inhibition of endoplasmic reticulum aminopeptidase 1 (ERAP1) suppresses free heavy chain expression and Th17 responses in ankylosing spondylitis.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 85 citations in OpenAlex.
- Exploring the Involvement ofLife (Basel, Switzerland) · 2026Review
- Mechanistic Insights from Human Studies in Axial Spondyloarthritis: A T Cell Story.Current rheumatology reports · 2026Review
- The Genetic Background of Ankylosing Spondylitis Reveals a Distinct Overlap with Autoimmune Diseases: A Systematic Review.Journal of clinical medicine · 2025Review
- ERAP1 Activity Modulates the Immunopeptidome but Also Affects the Proteome, Metabolism, and Stress Responses in Cancer Cells.Molecular & cellular proteomics : MCP · 2025Article
- HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity.Nature reviews. Rheumatology · 2025Review
- The Causal Relationships and Therapeutic Targets of Plasma Proteins in Ankylosing Spondylitis.Biomedicines · 2025Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- Exploring the Pathogenesis of Spondylarthritis beyond HLA-B27: A Descriptive Review.International journal of molecular sciences · 2024Review
- Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis.medRxiv : the preprint server for health sciences · 2024Article
- Sequence of Events in the Pathogenesis of Axial Spondyloarthritis: A Current Review-2023 SPARTAN Meeting Proceedings.Current rheumatology reports · 2024Review
- Polymorphic positions 349 and 725 of the autoimmunity-protective allotype 10 of ER aminopeptidase 1 are key in determining its unique enzymatic properties.Frontiers in immunology · 2024Article
- Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.Frontiers in immunology · 2024Article
- Uncovering the Underworld of Axial Spondyloarthritis.International journal of molecular sciences · 2023Review
- Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- How Has Molecular Biology Enhanced Our Undertaking of axSpA and Its Management.Current rheumatology reports · 2023Review
- Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.ACS pharmacology & translational science · 2022Review
- FunctionalCells · 2022Article
- The roles of Single Nucleotide Polymorphism (SNP) Endoplasmic Reticulum Aminopeptidase 1 (ERAP 1) gene in axial spondyloarthritis Indonesian adults.Annals of medicine and surgery (2012) · 2022Article
- Joint together: The etiology and pathogenesis of ankylosing spondylitis.Frontiers in immunology · 2022Review
- Spondyloarthritis: How far are we from precision medicine?Frontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveHuman leucocyte antigen (HLA)-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly associated with ankylosing spondylitis (AS). ERAP1 is a key aminopeptidase in HLA class I presentation and can potentially alter surface expression of HLA-B27 free heavy chains (FHCs). We studied the effects of ERAP1 silencing/inhibition/variations on HLA-B27 FHC expression and Th17 responses in AS.
methodsFlow cytometry was used to measure surface expression of HLA class I in peripheral blood mononuclear cells (PBMCs) from patients with AS carrying different ERAP1 genotypes (rs2287987, rs30187 and rs27044) and in ERAP1-silenced/inhibited/mutated HLA-B27-expressing antigen presenting cells (APCs). ERAP1-silenced/inhibited APCs were cocultured with KIR3DL2CD3ε-reporter cells or AS CD4+ T cells. Th17 responses of AS CD4+ T cells were measured by interleukin (IL)-17A ELISA and Th17 intracellular cytokine staining. FHC cell surface expression and Th17 responses were also measured in AS PBMCs following ERAP1 inhibition.
resultsThe AS-protective ERAP1 variants, K528R and Q730E, were associated with reduced surface FHC expression by monocytes from patients with AS and HLA-B27-expressing APCs. ERAP1 silencing or inhibition in APCs downregulated HLA-B27 FHC surface expression, reduced IL-2 production by KIR3DL2CD3ε-reporter cells and suppressed the Th17 expansion and IL-17A secretion by AS CD4+ T cells. ERAP1 inhibition of AS PBMCs reduced HLA class I FHC surface expression by monocytes and B cells, and suppressed Th17 expansion.
conclusionsERAP1 activity determines surface expression of HLA-B27 FHCs and potentially promotes Th17 responses in AS through binding of HLA-B27 FHCs to KIR3DL2. Our data suggest that ERAP1 inhibition has potential for AS treatment.
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