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

新诊断巨细胞动脉炎14-3-3蛋白自身抗体的特征及其与临床特征的关系

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作者:Anne Kistner, Marc B Bigler, Kathrin Glatz, Simon B Egli, Fabian S Baldin, Florian A Marquardsen, Matthias Mehling, Katharina M Rentsch, Daniel Staub, Markus Aschwanden, Mike Recher, Thomas Daikeler, Christoph T Berger

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.

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.

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