Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38475831", "kind": "science-record", "revision": 3, "content_hash": "sha256:142c1c1b4f5fbe10ef32e8cd3681516ac9c86fa309ee3728121c54268a49b185", "created_at": "2026-11-01T19:20:25Z", "updated_at": "2026-11-01T22:11:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics.", "doi": "10.1186/s12967-024-05077-y", "pmid": "38475831", "authors": ["Shuming Chen", "Weidi Huang", "Qiaoqian Wan", "Zichun Tang", "Xie Li", "Fang Zeng", "Shuyan Zheng", "Zhuo Li", "Xiao Liu"], "journal": "Journal of translational medicine", "year": 2024, "abstract": "BACKGROUND: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment.\nMETHODS: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved.\nRESULTS: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group.\nCONCLUSIONS: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.", "claims": [{"id": "claim-method", "statement": "Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38475831", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data used in this study are available in the public repository.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38475831", "locator": "sections[34] \"notes\" paragraph 1", "quote": "All the data used in this study are available in the public repository."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two proteins that are causally associated with AS and iridocyclitis are AIF1 and VARS, and AIF1 is causally associated with only acute and subacute iridocyclitis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38475831", "locator": "sections[19] \"MR analysis\" paragraph 4", "quote": "Two proteins that are causally associated with AS and iridocyclitis are AIF1 and VARS, and AIF1 is causally associated with only acute and subacute iridocyclitis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Two proteins that are causally associated with AS and iridocyclitis are AIF1 and VARS, and AIF1 is causally associated with only acute and subacute iridocyclitis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38475831"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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