PON1, A New Biomarker of Cardiovascular Disease, Is Low in Patients with Systemic Vasculitis Thomas Quéméneur, MD,* Françoise Martin-Nizard, PhD, † Abdelmejid Kandoussi, PhD, † Xavier Kyndt, MD,* Philippe Vanhille, MD,* Eric Hachulla, MD, PhD, ‡ Pierre-Yves Hatron, MD, ‡ Jean-Charles Fruchart, PhD, § Patrick Duriez, PhD, ¶ and Marc Lambert, MD, PhD  Objectives: Because systemic vasculitis (SV) predisposes to atherosclerosis, and high-density li- poprotein (HDL) prevents atherosclerosis by “reverse cholesterol transport” and by inhibiting low-density lipoprotein (LDL) oxidation thanks to apolipoprotein A-I (Apo-AI) and paraoxonase 1 (PON1), we assessed whether LDL oxidation was increased in SV and associated with less PON1 activity. Methods: The sera of 33 patients with active SV (ASV), 32 in full remission of SV (RSV) and 20 healthy subjects (HS) were analyzed for C-reactive protein (CRP), high-sensitivity-CRP, lipids, lipoproteins, apolipoproteins, PON1 activity, LDL-immune complexes (LDL-IC), and auto- antibodies to oxidized-LDL (ox-LDL), and anticardiolipin antibodies. Results: CRP was higher in ASV than RSV and HS, and negatively correlated with HDL-cholesterol and Apo-AI. Autoantibodies to ox-LDL and highly oxidized malondialdehyde-LDL were higher in RSV than ASV and HS (P  0.05). LDL-IC titers were higher in ASV than RSV and HS (P  0.05). PON1 activity was lower in ASV and RSV than HS (P = 0.02). A trend toward a negative correlation between basal PON1 activity and anti-MDA-LDL antibodies (P = 0.06) was observed. Conclusion: Inflammatory markers in SV were associated with a modified lipoprotein profile, which could lower PON1 activity and contribute to increased ox-LDL titers and accelerated atherosclerosis development. © 2007 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 37:149-155 Keywords: vasculitis, atherosclerosis, paraoxonase, oxidized-LDL, inflammation S ystemic vasculitis (SV) is a group of rare heteroge- neous systemic disorders characterized by inflam- mation, necrosis, and thrombosis of blood vessels (1). The pathological process, probably resulting from humoral and cellular immune-system abnormalities, is unknown. Atherosclerotic events often complicate its course, as indicated by in vivo, autopsy, and experimental findings (2-8). Interdependence between atherosclerosis development and the vasculitic process was suggested based on observations of a murine model of vasculitis (8). Atherosclerosis is an inflammatory disease that is influ- enced by free radicals and the oxidizing stress that they cause. According to the oxidative theory of atherosclero- sis, the atheromatous lesion is initiated by free radical- mediated oxidation of low-density lipoproteins (LDL), a process known as lipid peroxidation (9,10). *Hospital Staff Physician, Department of Nephrology and Internal Medicine, Hospital of Valenciennes, Valenciennes, France. †Associate Professor, Research Department on Lipoproteins and Atherosclerosis, INSERM U545, Pasteur Institute and University of Lille 2, Lille, France. ‡Professor of Medicine, Department of Internal Medicine, University Hospital and University of Lille 2, Faculty of Medicine, Lille, France. §Professor of Pharmacy, Research Department on Lipoproteins and Athero- sclerosis, INSERM U545, Pasteur Institute and University of Lille 2, Lille, France. ¶Professor of Pharmacy, Faculty of Pharmacy, University of Lille 2 and INSERM U545, Lille, France. Associate Professor, Department of Internal Medicine, University Hospital and University of Lille 2, Faculty of Medicine, Lille, France. Financial Support: none. The authors have no conflicts of interest to disclose. Address reprint requests to: Marc Lambert, MD, PhD, Service de Médecine Interne, CHRU de Lille, Hôpital Huriez, 1, place de Verdun, 59000, Lille, France. E-mail: m-lambert@chru-lille.fr. 149 0049-0172/07/$-see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2007.03.002