title: Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis.
abstract: In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States. Electronic address: apianta@mgh.harvard.edu.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pianta
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Elise E
authors.initials: EE
authors.lastname: Drouin
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Jameson T
authors.initials: JT
authors.lastname: Crowley
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Sheila
authors.initials: S
authors.lastname: Arvikar
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Klemen
authors.initials: K
authors.lastname: Strle
authors.affiliation: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, United States.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D017306:Annexin A2 / Q000276:immunology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D025065:Borrelia burgdorferi; D016022:Case-Control Studies; D049109:Cell Proliferation; D024881:Drug Resistance, Bacterial; D004797:Enzyme-Linked Immunosorbent Assay; D015787:Erythema Chronicum Migrans / Q000188:drug therapy / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008193:Lyme Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013583:Synovial Membrane / Q000166:cytology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D000900:Anti-Bacterial Agents; D001323:Autoantibodies; D007074:Immunoglobulin G
keywords: Annexin A2; Autoantigen; Borrelia burgdorferi; Lyme arthritis; Lyme disease