Characteristics of autoantibodies targeting 14-3-3 proteins and their association with clinical features in newly diagnosed giant cell arteritis

• Published in: Rheumatology (Oxford, England) Vol. 56; no. 5; p. kew469
• Main Authors: Kistner, Anne, Bigler, Marc B., Glatz, Kathrin, Egli, Simon B., Baldin, Fabian S., Marquardsen, Florian A., Mehling, Matthias, Rentsch, Katharina M., Staub, Daniel, Aschwanden, Markus, Recher, Mike, Daikeler, Thomas, Berger, Christoph T.
• Format: Journal Article
• Language: English
• Published: England 01.05.2017
• Subjects: 14-3-3 Proteins - immunology; Adult; Aged; Aged, 80 and over; Aortitis - immunology; Autoantibodies - metabolism; Biomarkers - metabolism; Female; Giant Cell Arteritis - diagnosis; Giant Cell Arteritis - immunology; Humans; Immunoglobulin G - metabolism; Male; Middle Aged; Stroke - immunology; Takayasu Arteritis - immunology; Toxoplasma - immunology; Toxoplasmosis - immunology; Vascular Remodeling - immunology; Young Adult; 14-3-3 proteins; giant cell arteritis; aortic aneurysm; multiplex; toxoplasmosis; large-vessel vasculitis; Takayasu’s arteritis; protein pulldown; autoantibodies; stroke
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kew469

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.