title: A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients With Lyme Disease.
abstract: To discover novel autoantigens associated with Lyme arthritis (LA), we identified T-cell epitopes presented in vivo by human leukocyte antigen (HLA)-DR molecules in patients' inflamed synovial tissue or joint fluid and tested each epitope for autoreactivity. Using this approach, we identified the highly expressed human protein, apolipoprotein B-100 (apoB-100), as a target of T- and B-cell responses in a subgroup of LA patients. Additionally, the joint fluid of these patients had markedly elevated levels of apoB-100 protein, which may contribute to its autoantigenicity. In patients with antibiotic-refractory LA, the magnitude of apoB-100 antibody responses correlated with increased numbers of plasma cells in synovial tissue, greater numbers and activation of endothelial cells, and more synovial fibroblast proliferation. Thus, a subset of LA patients have high levels of apoB-100 in their joints and autoreactive T- and B-cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School.
authors.forename: Jameson T
authors.initials: JT
authors.lastname: Crowley
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School.
authors.forename: Elise E
authors.initials: EE
authors.lastname: Drouin
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pianta
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School.
authors.forename: Klemen
authors.initials: K
authors.lastname: Strle
authors.affiliation: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Massachusetts.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Massachusetts.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D053299:Apolipoprotein B-100 / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D025065:Borrelia burgdorferi; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008193:Lyme Disease / Q000453:epidemiology / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D053299:Apolipoprotein B-100; D001324:Autoantigens
keywords: Borrelia burgdorferi; Lyme arthritis; Lyme disease; apolipoprotein B; autoantibodies; autoimmunity; erythema migrans