Antibodies to high‐density lipoprotein and β₂‐glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome

Abstract

Objective. To determine the prevalence of antihigh-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-␤ 2 -glycoprotein I (anti-␤ 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-␤ 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-␤ 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).Conclusion. IgG anti-HDL and IgG anti-␤ 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.

Antiphospholipid Antibodies and Their Association with Atherosclerotic Changes in Patients with Systemic Lupus Erythematosus – Review of Literature and Own Experiences

“…However, on the basis on multiple regression model only aβ2-GPI IgG were found an independent predictor of decreased paraoxonase activity (r= -0.483, p = 0.003). The reported interactions may be relevant to the development of atherosclerosis in SLE and PAPS (Delgado Alves et al, 2002). Other observations also supported findings on the role of paraoxonase activity in SLE-related vascular abnormalities.…”

“…However, study performed in subjects with idiopathic aPL showed association between aCL IgG titre and CIMT. In addition, it confirmed aCL IgG as well as homocysteine and fibrinogen as independent predictors of CIMT indicating that measurement of homocysteine and fibrinogen may help to identify aPL patients who are more likely to develop atherosclerosis (Ames et al, 2002). More recent studies also confirmed a usefulness of CIMT measurement in a detection of early atherosclerotic changes and showed an association between CIMT and aPL in thrombotic PAPS patients (Ames et al, 2009a) as well as in patients with APS secondary to SLE (Belizna et al, 2008).…”

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

“…Indeed, the microbiota of inflammatory bowel disease (IBD) patients has a low abundance of Faecalibacterium prausnitzii, a member of this phylum with a known and well characterized anti-inflammatory effect (34)(35)(36)(37). In spite of the fact that the absence of differences in total antioxidant capacity between SLE and controls is in agreement with previous studies in SLE subjects (38,39), there is no consensus about it in the literature. While some authors have reported lower levels in autoimmune diseases (40,41), others have found higher ones (42).…”

Severe Thromboembolism and Systemic Lupus Erythematosus Developing after Ovarian Hyperstimulation in a Persistent Carrier of Antiphospholipid Antibodies

“…The latter study also showed that the elevated PL titre was negatively related to the antioxidant capacity of PON [17]. PON accounts for most of the antioxidant of properties of HDL against LDL oxidation [18] and its activity is known to be decreased in PAPS [19].…”