Identification of target antigens of anti-endothelial cell antibodies in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides: A proteomic approach |
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Authors: | Alexis Ré gent,Sé bastien Lofek,Hanadi Dib,Guillaume Bussone,Nicolas Tamas,Christian Federici,Cé dric Broussard,Loï c Guillevin,Luc Mouthon |
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Affiliation: | 1. Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France;2. Pôle de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, F-75679 Paris Cedex 14, France;3. Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Méchain, 75014 Paris, France |
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Abstract: | Anti-endothelial cell antibodies (AECAs) have been reported to cause endothelial cell dysfunction, but their specific targets have never been identified in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Proteins from human umbilical vein endothelial cells (HUVECs) were separated by 2-dimensional electrophoresis (2-DE). 2-D immunoblots were used to compare serum IgG reactivities from 30 patients with AAV and 12 healthy controls (HCs). Proteins identified as target antigens by MALDI- TOF-TOF mass spectrometry included lamin A/C, vimentin, α-enolase, far upstream binding protein 2 (FUBP2) and protein disulfide-isomerase A3 precursor (PDIA3). Antibodies targeting lamin A, vimentin, α-enolase, FUBP2 and PDIA3 were identified in 57.1%, 64.3%, 35.7%, 50% and 0% of patients with microscopic polyangiitis and 8%, 3.3%, 7.2%, 0% and 6.7% of HCs respectively. IgG from patients with microscopic polyangiitis had stronger reactivity against HUVEC than other groups and HCs and induced stronger Erk phosphorylation in HUVECs than IgG from HCs. |
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Keywords: | Anti-neutrophil cytoplasmic antibodies Autoantibodies Human umbilical vein endothelial cell Vasculitides Lamin Erk |
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