ArticleArthritis & rheumatology (Hoboken, N.J.)2018
The Role of Autophagy in the Degradation of Misfolded HLA-B27 Heavy Chains.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Restoring immune homeostasis in the spinal microenvironment: targeting mechano-inflammation and immunometabolic reprogramming.Frontiers in immunology · 2026Review
- Rapamycin treatment ameliorates HLA-B27-mediated gut inflammation and alters the microbiome in experimental spondyloarthritis.Frontiers in immunology · 2026Article
- HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity.Nature reviews. Rheumatology · 2025Review
- Gut microbiota and ankylosing spondylitis: current insights and future challenges.Microbial cell (Graz, Austria) · 2025Review
- Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response.Frontiers in cell and developmental biology · 2025Review
- CHOP-mediated IL-23 overexpression does not drive colitis in experimental spondyloarthritis.Scientific reports · 2024Article
- Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration.Journal of translational medicine · 2023Article
- 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
- Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies.Cells · 2022Review
- Joint together: The etiology and pathogenesis of ankylosing spondylitis.Frontiers in immunology · 2022Review
- MicroRNAs in Axial Spondylarthritis: an Overview of the Recent Progresses in the Field with a Focus on Ankylosing Spondylitis and Psoriatic Arthritis.Current rheumatology reports · 2021Review
- Ankylosing spondylitis: an autoimmune or autoinflammatory disease?Nature reviews. Rheumatology · 2021Review
- The enigmatic role of HLA-B*27 in spondyloarthritis pathogenesis.Seminars in immunopathology · 2021Review
- Lessons on SpA pathogenesis from animal models.Seminars in immunopathology · 2021Review
- Aberrant antigen processing and presentation: Key pathogenic factors leading to immune activation in Ankylosing spondylitis.Seminars in immunopathology · 2021Review
- Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27.Frontiers in immunology · 2021Article
- Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The "Out of the Box" View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF).Frontiers in medicine · 2021Review
- Understanding the Pathogenesis of Spondyloarthritis.Biomolecules · 2020Review
- Degradation of proteins by PROTACs and other strategies.Acta pharmaceutica Sinica. B · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo determine whether autophagy is involved in the degradation of misfolded HLA-B27 in experimental spondyloarthritis.
methodsBone marrow-derived macrophages from HLA-B27/human β
resultsHLA-B27-expressing macrophages showed phosphatidylethanolamine-conjugated microtubule-associated protein 1 light chain 3B levels similar to those in both control groups, before and after manipulation of autophagy. Blocking autophagic flux with bafilomycin resulted in the accumulation of misfolded HLA-B27 dimers and oligomers as well as monomers, which was comparable with the results of blocking endoplasmic reticulum-associated degradation (ERAD) with the proteasome inhibitor bortezomib. HLA-B7 monomers also accumulated after blocking each degradation pathway. The ubiquitin-to-heavy chain ratio was 2-3-fold lower for HLA-B27 than for HLA-B7. Activation of autophagy with rapamycin rapidly eliminated ~50% of misfolded HLA-B27, while folded HLA-B27 or HLA-B7 monomeric heavy chains were minimally affected.
conclusionThis study is the first to demonstrate that both autophagy and ERAD play roles in the elimination of excess HLA class I heavy chains expressed in transgenic rats. We observed no evidence that HLA-B27 expression modulated the autophagy pathway. Our results suggest that impaired ubiquitination of HLA-B27 may play a role in the accumulation of misfolded disulfide-linked dimers, the elimination of which can be enhanced by activation of autophagy. Manipulation of the autophagy pathway should be further investigated as a potential therapeutic target in spondyloarthritis.
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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.