Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus

• Published in: Rheumatology (Oxford, England) Vol. 48; no. 1; pp. 26 - 31
• Main Authors: Batuca, J. R., Ames, P. R. J., Amaral, M., Favas, C., Isenberg, D. A., Delgado Alves, J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2009; Oxford Publishing Limited (England)
• Subjects: Adult; Antibodies against Apolipoprotein A-I; Antibodies against high-density lipoprotein; Antioxidants - analysis; Apolipoprotein A-I - immunology; Aryldialkylphosphatase - blood; Autoantibodies - blood; Biological and medical sciences; Biomarkers - blood; Diseases of the osteoarticular system; Endothelial dysfunction; Female; Humans; Immunoglobulin G - blood; Intercellular Adhesion Molecule-1 - blood; Lipids - blood; Lipoproteins, HDL - immunology; Lupus Erythematosus, Systemic - immunology; Male; Medical sciences; Middle Aged; Nitric oxide; Nitric Oxide - blood; Paraoxonase; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index; Systemic lupus; Vascular Cell Adhesion Molecule-1 - blood; Young Adult; Endothelial dysfunction; Paraoxonase; Antibodies against Apolipoprotein A-I; Nitric oxide; Systemic lupus; Antibodies against high-density lipoprotein; Immunopathology; Connective tissue disease; Skin disease; Antibody; Rheumatology; Autoimmune disease; Endothelium; Apolipoprotein A; Systemic lupus erythematosus; Systemic disease; Disseminated; Lipoprotein HDL
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ken397

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.