Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome.
OBJECTIVE
To determine the prevalence of anti-high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS).


METHODS
Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-beta(2)GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL(2), and HDL(3) were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence.


RESULTS
Levels of total HDL, HDL(2), and HDL(3) were reduced in patients with SLE compared with controls (mean +/- SD 0.51 +/- 0.3, 0.37 +/- 0.3, and 0.14 +/- 0.1 mmoles/liter, respectively, versus 1.42 +/- 0.9, 1.01 +/- 0.7, and 0.40 +/- 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = -0.48, P = 0.005) whereas in the primary APS population, IgG anti-beta(2)GPI was the only independent predictor of PON activity (r = -0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = -0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02).


CONCLUSIONS
IgG anti-HDL and IgG anti-beta(2)GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.
Delgado Alves
J
J
Windeyer Institute of Medical Sciences, Room 118-Centre for Rheumatology, University College of London, 46 Cleveland Street, London W1T 4JF, UK. j.alves@ucl.ac.uk
Ames
P R J
PR
Donohue
S
S
Stanyer
L
L
Nourooz-Zadeh
J
J
Ravirajan
C
C
Isenberg
D A
DA
Noorouz-Zadeh
J
J
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000975:Antioxidants / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism; D043303:Aryldialkylphosphatase; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood; D004950:Esterases / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000276:immunology; D012044:Regression Analysis; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000975:Antioxidants; D015415:Biomarkers; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D053482:beta 2-Glycoprotein I; D011516:Prothrombin; D002784:Cholesterol; D004950:Esterases; D043303:Aryldialkylphosphatase