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Open Access Research article

Identification of target antigens of anti-endothelial cell and anti-vascular smooth muscle cell antibodies in patients with giant cell arteritis: a proteomic approach

Alexis Régent123, Hanadi Dib12, Kim H Ly124, Christian Agard5, Mathieu C Tamby12, Nicolas Tamas12, Babette Weksler6, Christian Federici12, Cédric Broussard7, Loïc Guillevin23 and Luc Mouthon123*

Author Affiliations

1 Inserm U1016, Institut Cochin, CNRS UMR 8104, 8 rue Méchain, F-75014 Paris, France

2 Université Paris Descartes, 12 rue de l'Ecole de Médecine, F-75270 Paris, France

3 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 Paris, France

4 Service de Médecine Interne A, CHU Dupuytren, 2 avenue Martin Luther King, F-87042 Limoges cedex 1, France

5 Service de Médecine Interne, hôpital Hôtel Dieu, Place Alexis Ricordeau, F-44093 Nantes cedex 1, France

6 Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA

7 Institut Cochin, Plate-forme Protéomique de l'Université Paris Descartes, CNRS UMR 8104, 8 rue Méchain, F-75014 Paris, France

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Arthritis Research & Therapy 2011, 13:R107  doi:10.1186/ar3388

Published: 28 June 2011

Abstract

Introduction

Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to identify their target antigens.

Methods

Sera from 15 GCA patients were tested in 5 pools of 3 patients' sera and compared to a sera pool from 12 healthy controls (HCs). Serum immunoglobulin G (IgG) reactivity was analysed by 2-D electrophoresis and immunoblotting with antigens from human umbilical vein ECs (HUVECs) and mammary artery VSMCs. Target antigens were identified by mass spectrometry.

Results

Serum IgG from GCA patients recognised 162 ± 3 (mean ± SD) and 100 ± 17 (mean ± SD) protein spots from HUVECs and VSMCs, respectively, and that from HCs recognised 79 and 94 protein spots, respectively. In total, 30 spots from HUVECs and 19 from VSMCs were recognised by at least two-thirds and three-fifths, respectively, of the pools of sera from GCA patients and not by sera from HCs. Among identified proteins, we found vinculin, lamin A/C, voltage-dependent anion-selective channel protein 2, annexin V and other proteins involved in cell energy metabolism and key cellular pathways. Ingenuity pathway analysis revealed that most identified target antigens interacted with growth factor receptor-bound protein 2.

Conclusions

IgG antibodies to proteins in the proteome of ECs and VSMCs are present in the sera of GCA patients and recognise cellular targets that play key roles in cell biology and maintenance of homeostasis. Their potential pathogenic role remains to be determined.