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

Autor:	Kistner A; Translational Immunology, Department of Biomedicine., Bigler MB; Translational Immunology, Department of Biomedicine., Glatz K; Department of Pathology., Egli SB; Translational Immunology, Department of Biomedicine., Baldin FS; Department of Biomedicine, Immunodeficiency Laboratory., Marquardsen FA; Department of Biomedicine, Immunodeficiency Laboratory., Mehling M; Translational Neuroimmunology, Department of Biomedicine., Rentsch KM; Laboratory Medicine., Staub D; Department of Angiology., Aschwanden M; Department of Angiology., Recher M; Department of Biomedicine, Immunodeficiency Laboratory.; Immunodeficiency Clinic., Daikeler T; Rheumatology Clinic., Berger CT; Translational Immunology, Department of Biomedicine.; Medical Outpatient Clinic, Department of Internal Medicine, University Basel Hospital, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2017 May 01; Vol. 56 (5), pp. 829-834.
DOI:	10.1093/rheumatology/kew469
Abstrakt:	Objectives: 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. Methods: 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. Results: 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. Conclusion: 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. (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)
Databáze:	MEDLINE
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