ArticleScientific reports2019
Interactions of HLA-DR and Topoisomerase I Epitope Modulated Genetic Risk for Systemic Sclerosis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Human-murine chimeric autoantibodies with high affinity and specificity for systemic sclerosis.Frontiers in immunology · 2023Article
- Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis.NPJ genomic medicine · 2022Article
- High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD).Scientific reports · 2022Article
- Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders.Frontiers in medicine · 2020Review
- Lymphocyte proliferation induced by high-affinity peptides for HLA-B*51:01 in Behçet's uveitis.PloS one · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The association of systemic sclerosis with anti-Topoisomerase 1 antibody (ATASSc) with specific alleles of human leukocyte antigen (HLA)-DR has been observed among various ethnics. The anti-Topoisomerase 1 antibody is a common autoantibody in SSc with diffuse cutaneous scleroderma, which is one of the clinical subtypes of SSc. On the other hand, an immunodominant peptide of topoisomerase 1 (Top1) self-protein (residues 349-368) was reported to have strong association with ATASSc. In this study, molecular dynamics simulation was performed on the complexes of Top1 peptide with various HLA-DR subtypes divided into ATASSc-associated alleles (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), suspected allele (HLA-DRB5*01:02), and non-associated allele (HLA-DRB1*01:01). The unique interaction for each system was compared to the others in terms of dynamical behaviors, binding free energies and solvation effects. Our results showed that three HLA-DR/Top1 complexes of ATASSc association mostly exhibited high protein stability and increased binding efficiency without solvent interruption, in contrast to non-association. The suspected case (HLA-DRB5*01:02) binds Top1 as strongly as the ATASSc association case, which implied a highly possible risk for ATASSc development. This finding might support ATASSc development mechanism leading to a guideline for the treatment and avoidance of pathogens like Top1 self-peptide risk for ATASSc.
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