title: Characteristics of autoantibodies targeting 14-3-3 proteins and their association with clinical features in newly diagnosed giant cell arteritis.
abstract: Autoantibodies are useful biomarkers for diagnosing and monitoring treatment in some autoimmune diseases. Antibodies against isoforms of 14-3-3 protein have been proposed as biomarkers for the presence of aortic aneurysm in large-vessel vasculitis (LVV). Here, we aimed to evaluate the diagnostic role and potential immunopathological involvement of anti-14-3-3 antibodies in newly diagnosed LVV patients.
  
  
  
  Antibodies against three isoforms of 14-3-3 (γ, ɛ and ζ) were measured in 90 subjects: 48 GCA and 3 Takayasu's arteritis (TA) patients, and 39 controls (non-inflammatory and inflammatory diseases), using a multiplexed bead-based immunoassay and immunoprecipitation studies. The positive cut-off value was defined based on young healthy controls. Anti-14-3-3 IgG antibodies in LVV patients were compared with those in controls in order to assess their diagnostic performance, and the relationship of anti-14-3-3 IgG antibodies to the immunohistopathology of artery explants was assessed.
  
  
  
  Antibodies against all three 14-3-3 isoforms were detected in LVV patients as well as in age-matched inflammatory and non-inflammatory controls. Among LVV patients, detection of antibodies targeting 14-3-3 ɛ and ζ was associated with more severe disease. Detection of antibodies against 14-3-3 γ was linked to latent Toxoplasma gondii infection, a parasite that secrets a 14-3-3 homologue, suggesting potential cross-reactivity.
  
  
  
  Detection of antibodies against 14-3-3 proteins at the time of LVV diagnosis is not disease-specific. Their presence at high levels in LVV patients with stroke, aortitis and-in a previous study-aneurysm formation may indicate an association with extensive tissue destruction. The relevance of 14-3-3 antibodies in non-LVV patients needs to be investigated in larger cohorts.
authors.affiliation: Translational Immunology, Department of Biomedicine.
authors.forename: Anne
authors.initials: A
authors.lastname: Kistner
authors.affiliation: Translational Immunology, Department of Biomedicine.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bigler
authors.affiliation: Department of Pathology.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Glatz
authors.affiliation: Translational Immunology, Department of Biomedicine.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Egli
authors.affiliation: Department of Biomedicine, Immunodeficiency Laboratory.
authors.forename: Fabian S
authors.initials: FS
authors.lastname: Baldin
authors.affiliation: Department of Biomedicine, Immunodeficiency Laboratory.
authors.forename: Florian A
authors.initials: FA
authors.lastname: Marquardsen
authors.affiliation: Translational Neuroimmunology, Department of Biomedicine.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mehling
authors.affiliation: Laboratory Medicine.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Rentsch
authors.affiliation: Department of Angiology.
authors.forename: Daniel
authors.initials: D
authors.lastname: Staub
authors.affiliation: Department of Angiology.
authors.forename: Markus
authors.initials: M
authors.lastname: Aschwanden
authors.affiliation: Department of Biomedicine, Immunodeficiency Laboratory.|Immunodeficiency Clinic.
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.affiliation: Rheumatology Clinic.
authors.forename: Thomas
authors.initials: T
authors.lastname: Daikeler
authors.affiliation: Translational Immunology, Department of Biomedicine.|Medical Outpatient Clinic, Department of Internal Medicine, University Basel Hospital, Basel, Switzerland.
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Berger
mesh_terms: D048948:14-3-3 Proteins / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001025:Aortitis / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000276:immunology; D013625:Takayasu Arteritis / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology; D066253:Vascular Remodeling / Q000276:immunology; D055815:Young Adult
chemical_list: D048948:14-3-3 Proteins; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G
keywords: 14-3-3 proteins; Takayasu’s arteritis; aortic aneurysm; autoantibodies; giant cell arteritis; large-vessel vasculitis; multiplex; protein pulldown; stroke; toxoplasmosis