Background/Purpose: SLE is a chronic autoimmune inflammatory disease. Increasing evidence suggest that excess production of reactive oxygen species (ROS) may cause oxidative stress and favor the development of immune-cell dysfunction, autoantigen production and autoantibody development. Oxidized-lipids have chemotactic, immune-stimulatory, and toxic properties and play an important role in the pathogenesis of atherosclerosis and kidney injury in SLE. In the current study, we evaluated the serum levels of oxidized-lipids and their autoantibodies in SLE patients and identified the relationships between oxidized-lipids, auto-antibodies and disease.

Methods: Serum MDA was measured by a colorimetric method and HODE was assayed by mass spectrometry. Serum levels of specific oxidized-LDL immune complex (ox-LDL-IC), autoantibodies to ds-DNA, ox-LDL, MDA-LDL, 9-HODE (9-hydroxy-10,12-octadecadienoic acid), 13-HODE (13-hydroxy-9,11-octadecadienoic acid), POVPC (1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine) were detected by ELISA in 64 SLE patients (37 with active SLE, SLEDAI > 6) and 9 healthy controls. 

Results:  (1) Active SLE patients exhibited increased serum levels of anti-ds-DNA-IgG (0.349±0.039 vs 0.115±0.018; p=0.0001), anti-MDA-LDL-IgG (1049.0±116.2 ku/L vs 468.7±103.6 ku/L; p=0.003), anti-LDL-IgG (1368.0±183.6 EU/ml vs 654.0±87.17 EU/ml; p=0.004), anti-9-HODE-IgG (0.632±0.044 vs 0.298±0.058; p=0.001), anti-13-HODE-IgG (0.542±0.047 vs 0.251±0.048; p=0.0003), anti-POVPC-IgG (0.429±0.030 vs 0.297±0.030; p=0.001) and ox-LDL-IC (0.375±0.018 vs 0.270±0.022; p=0.003) compared to healthy controls, but decreased serum levels of anti-9-HODE-IgM (0.257±0.016 vs 0.335±0.032; p=0.019) and anti-13-HODE-IgM (0.336±0.025 vs 0.441±0.042; p=0.029). (2) Serum HODE levels were positively correlated with proteinuria (r=0.68/p=0.002), CRP (r=0.51/p=0.03) and ox-LDL-IC (r=0.45/p=0.04). Serum anti-ox-LDL-IgG was positively correlated with SLEDAI (r=0.34/p=0.02), and negatively with C3 (r= -0.39/p=0.01). Anti-9-HODE-IgG was positively correlated with SLEDAI (r=0.27/p=0.02), and negatively with C4 (r= -0.3/p=0.01). Anti-POVPC-IgG was positively correlated with SLEDAI (r=0.23/p=0.04), and negatively with C4 (r= -0.27/p=0.03). 

Conclusion: Active SLE patients exhibit significantly increased serum levels of IgG anti-oxidized-lipid autoantibodies. Taken together with our recent metabolomic screen indicating that oxidized lipids are also elevated in SLE sera (PLOS ONE, June 2012), the current findings suggest that coordinate elevation of oxidized lipids, autoantibodies to these lipids, and immune complexes of these antigen-antibody components could serve as potential serum markers of disease activity in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-complexes-and-autoantibodies-to-oxidized-lipids-in-systemic-lupus-erythematosus/