ArticleArthritis and rheumatism2013
A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 91 citations in OpenAlex.
- Infection-Triggered Immune Dysregulation and Immunopathology in Lyme Disease: Mechanisms and Clinical Implications.Journal of clinical medicine · 2026Review
- Lyme borreliosis.Nature reviews. Disease primers · 2026Review
- Article
- Aspects of the Immunopathogenesis of Lyme Arthritis.Microorganisms · 2025Review
- HLA-DR-Expressing Fibroblast-Like Synoviocytes Are Inducible Antigen Presenting Cells That Present Autoantigens in Lyme Arthritis.ACR open rheumatology · 2024Article
- Identification of Major Histocompatibility Complex Class II Epitopes From Lyme Autoantigen Apolipoprotein B-100 and Borrelia burgdorferi Mcp4 in Murine Lyme Arthritis.The Journal of infectious diseases · 2024Article
- Lyme Arthritis: A 50-Year Journey.The Journal of infectious diseases · 2024Article
- Variants in the Late Cornified Envelope Gene Locus Are Associated With Elevated T-helper 17 Responses in Patients With Postinfectious Lyme Arthritis.The Journal of infectious diseases · 2024Article
- Synthesis of aMolecules (Basel, Switzerland) · 2024Article
- Antigenicity and immunogenicity of different morphological forms of Borrelia burgdorferi sensu lato spirochetes.Scientific reports · 2024Article
- Human leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis.bioRxiv : the preprint server for biology · 2023Article
- Autoimmunity to synovial extracellular matrix proteins in patients with postinfectious Lyme arthritis.The Journal of clinical investigation · 2023Article
- Cell-Mediated Cytotoxicity in Lyme Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Lyme disease and the pursuit of a clinical cure.Frontiers in medicine · 2023Review
- Lyme Arthritis.Infectious disease clinics of North America · 2022Review
- Seroprevalence of Antibodies against Tick-Borne Pathogens in Czech Patients with Suspected Post-Treatment Lyme Disease Syndrome.Microorganisms · 2021Article
- Article
- Lyme arthritis: linking infection, inflammation and autoimmunity.Nature reviews. Rheumatology · 2021Review
- The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete.PLoS pathogens · 2021Article
- Immune Response toCurrent issues in molecular biology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveAutoantigen presentation by HLA-DR molecules is thought to be a central component of many autoimmune diseases, but identifying disease-relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic-refractory Lyme arthritis, in which infection-induced autoimmunity is thought to play an important role.
methodsUsing tandem mass spectrometry, naturally presented HLA-DR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera.
resultsOf 120 HLA-DR-presented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in ∼10-30% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritis-associated HLA-DR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic-responsive arthritis, those with antibiotic-refractory arthritis had significantly higher concentrations of ECGF in synovial fluid (P<0.0001) and more often had ECGF antibody reactivity. Among non-antibiotic-treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis.
conclusionT and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic-refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness.
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