Background/Purpose:

Oxidized low-density lipoprotein (oxLDL), a key molecule in atherogenesis, serves as the source of anionic charged particles that bind to beta2glycoprotein I (Β₂GPI) and reinforces procoagulant activity or concomitant atherosclerosis in the presence of antiphospholipid antibodies(aPL). High density lipoprotein (HDL) is the major molecule not only blocks arteriosclerotic/procoagulant function of oxLDL but helps prevent LDL from oxidation with the assistance of HDL-associated proteins such as paraoxonase type 1 (PON-1) and apolipoprotein A-1 (ApoA-1).In antiphospholipid syndrome(APS), as well as in systemic lupus erythematosus (SLE), autoantibodies against HDL are prevalent and inversely correlate with serum HDL levels which may in turn, be associated with the production of oxLDL. In this study, we identified autoantibodies against HDL(aHDL), PON-1(aPON-1) or ApoA-1(aApoA-1) and explored their correlations with oxLDL in patients with APS.

Methods:

This study was designed as a retrospective and cross-sectional study and comprised a total of consecutive patients with primary APS (PAPS) (n=24),SLE (n= 47) and non-lupus connective tissue diseases (others)(n=19) who visited Hokkaido University Hospital Rheumatology clinic during 2009 and 2012. Blood samples of 52 healthy controls (healthy) were also investigated. Lupus anticoagulant assays and aPL ELISAs (IgG/M of anticardiolipin antibodies, anti-Β₂GPI antibodies and phosphatidylserine dependent antiprothrombin antibodies) were performed in all patients.In-hose ELISA was used to detect aHDL, aApo-A1 and aPON-1 according to the previous report (Batuca et al, Rheumatology(Oxford), 2009). Serum oxLDL levels were measured with a commercial ELISA (MDA-oxLDL, Human, ELISA Kit,Biomedica, UK). Kruskal-Wallis test was employed to analyze the data of three or more groups

Results:

Among the patient groups, serum levels of lipoproteins (LDL, HDL) and the prevalence of statin treatment were comparable, while serum levels of oxLDL were significantly elevated in PAPS (PAPS vs. SLE vs. others (mean+/-2SD): 3.27+/-6.89 vs. 1.69+/- 4.35 vs. 0.8 +/- 3.72 mg/ml, p<0.05). Titers of aHDL were similar among the patient groups, while the titers of aApo-A1 and aPON-1 were significantly elevated in PAPS (aAPO-A1vs. PAPS vs. SLE vs. others vs. healthy (means +/-2SD) 0.93+/-0.63 vs. 0.63+/-0.94 vs. 0.45+/-0.50 vs. 0.42+/-0.96 mg/ml p<0.002) ( aPON-1: PAPS vs. SLE vs. others vs. healthy(mean+/-2SD) 148+/-182 vs. 116 +/- 196 vs. 72.6 +/- 156 %positive control, p<0.005). In PAPS, patients with positive ( over healthy control 99 percentile) aAPO-A1 and aPON-1 were significantly prevalent. Either antibody was positive in 14/24 of PAPS, whilst in SLE and others were 14/47 and 7/19, respectively (p<0.01). Double positivity ( aApo-A1 and aPON-1) was found in 5/24 PAPS, 5/47 SLE and 1/19 in others(p<0.01). None of the aPL or total aPL titers (aPL scores) correlated with autoantibodies related to HDL nor with oxLDL levels.

Conclusion:

Elevated oxLDL in PAPS may be one of the causal mechanisms of the disease and might be consequence of the impairment of the antioxidant function of HDL induced by the presence of aApoA-I and aPON .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-against-high-density-lipoprotein-associated-proteins-are-related-to-elevated-oxidized-low-density-lipoprotein-levels-in-antiphospholipid-syndrome/