Rheumatology Advance Access originally published online on November 10, 2008
Rheumatology 2009 48(1):26-31; doi:10.1093/rheumatology/ken397
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Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus
1Pharmacology Department, Faculty of Medical Sciences of Lisbon, Lisbon, Portugal, 2Immunoclot Ltd, Leeds, UK, 3Autoimmune Diseases Unit, Curry Cabral Hospital, Lisbon, Portugal, 4Centre for Rheumatology, University College London, London, UK.
Correspondence to: J. Delgado Alves, Departamento de Farmacologia, Faculdade de Ciências Médicas, Campo Mártires da Pátria, 130, 1169-056 Lisboa, Portugal. E-mail: jose.alves{at}fcm.unl.pt
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Abstract |
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Objective. To determine whether antibodies against high-density lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with the anti-atherogenic functions of high-density lipoprotein (HDL) and relate to disease activity and damage in SLE.
Methods. Seventy-seven SLE patients were compared with an age- and sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG aApoA-I, soluble vascular cell and intracellular cell adhesion molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA, paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx) metabolites by the Griess reaction, and total anti-oxidant capacity (TAC) by chemiluminescence.
Results. Compared with controls, SLE patients showed higher titres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P < 0.0001), lower PON activity (P < 0.0001), increased NOx (P < 0.0001), VCAM-1 (P < 0.0001) and ICAM-1 (P = 0.0008) and lower TAC (P = 0.0006). Titres of IgG aHDL positively correlated with IgG aApo A-I (r = 0.64, P < 0.0001), NOx (r = 0.32, P = 0.007), inversely correlated with PON activity (r = –0.34, P = 0.002) and TAC (r = –0.43, P = 0.0004) and were independently associated with ICAM-1 (t = 3.509, P = 0.001). IgG aApo A-I titres correlated positively with NO (r = 0.37, P = 0.007), inversely with PON activity (r = –0.31, P = 0.006), TAC (r = –0.47, P < 0.0001) and were independently associated with HDL (t = –2.747, P = 0.008) and VCAM-1 (t = 3.311, P = 0.002), the latter alongside NOx (T = 2.271, P = 0.02). Elevated titres of IgG aHDL and IgG aApo A-I and reduced PON activity related to increased disease score (BILAG) and damage index (SLICC/ACR DI).
Conclusion. In SLE, IgG aHDL and aApo A-I associate with disease activity and damage and interfere with the anti-oxidant and anti-inflammatory functions of HDL favouring atherogenesis.
KEY WORDS: Systemic lupus, Antibodies against high-density lipoprotein, Antibodies against Apolipoprotein A-I, Paraoxonase, Nitric oxide, Endothelial dysfunction
Submitted 6 March 2008;
revised version accepted 15 September 2008.
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  M. Charakida, C. Besler, J. R. Batuca, S. Sangle, S. Marques, M. Sousa, G. Wang, D. Tousoulis, J. Delgado Alves, S. P. Loukogeorgakis, et al. Vascular Abnormalities, Paraoxonase Activity, and Dysfunctional HDL in Primary Antiphospholipid Syndrome JAMA, September 16, 2009; 302(11): 1210 - 1217. [Abstract] [Full Text] [PDF]
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