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Increased atherosclerotic plaque and anti-oxidized low density lipoprotein in anti-Ro60 SLE autoantibody subset

Kurien, B. T.; Fesmire, J.; Nath, S. K.; Scofield, R. H.

2023-04-05 biochemistry
10.1101/2023.04.04.535634 bioRxiv
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ObjectivePremature atherosclerosis is associated with systemic lupus erythematosus (SLE). We previously showed an association of anti-Ro60/La/Ro52 to anti-oxidized LDL in SLE. Here, we hypothesized that atherosclerotic plaque will be associated with anti-oxidized LDL (anti-oxLDL)/anti-lipoprotein lipase (ALPL) in a specific SLE autoantibody sub-set (anti-Ro60 positive, anti-RNP positive or extractable nuclear antigen antibody negative). MethodsWe carried out a case-control study (one time-point testing) of plaque, ALPL, anti-oxLDL, anti-low density lipoprotein (ALDL) or anti-LDL in 114 SLE and 117 age/sex matched controls. Total cholesterol, LDL, HDL, triglycerides, and HDL-Trig were also measured. Students t test was used for statistical analysis ResultsInterestingly, plaque was highest in SLE subset with anti-Ro60 (23/114). Plaque and anti-oxLDL were statistically significantly elevated in the anti-Ro60 SLE subset (1.3 +/-1.66, p<0.01; 0.26 +/-0.16, p<0.002 respectively) compared to controls (0.54 +/-1.26; 0.165 +/-0.13 respectively), but not anti-LPL/anti-LDL. Plaque was significantly elevated (0.9 +/-1.71; p< 0.05) in the SLE subset without anti-ENA (63/114) compared to controls. Other antibodies in this subset were not statistically different compared to other SLE subsets or controls. Only anti-oxLDL was significantly elevated (0.29 +/-0.27; p<0.005) in SLE subset with anti-RNP (14/114) compared to controls, while none were elevated in anti-SmRNP subset (6/114). We did not find significant differences in lipids between various SLE subsets. ConclusionPlaque segregates in anti-Ro and ENA negative groups either with or without anti-oxLDL. It will be clinically important if cardiovascular events are augmented in SLE anti-Ro subset having elevated anti-oxidized LDL antibodies. Key pointsO_LIPlaque and anti-oxLDL significantly elevated in anti-Ro60 SLE subset C_LIO_LIOnly plaque significantly elevated in SLE subset without antibodies against extractable nuclear antigens C_LIO_LIIt will be clinically important to see if augmented cardiovascular events occur in SLE anti-Ro subset having elevated anti-oxidized LDL antibodies. C_LI

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