Background/Purpose:   Human apoM is a 25kDa apolipoprotein present in 5% of HDL particles in plasma. In mouse models, apoM is antiatherogenic and vasculoprotective and seems to play a role in keeping endothelial barrier integrity. In SLE, decreased plasma levels of anti-oxidant and anti-inflammatory HDL may contribute to the development of atherosclerosis. The aims of the current study were to determine the impact of SLE disease activity and different organ manifestations on apoM levels and investigate if apoM levels reflect endothelial function in SLE.

Methods:   Plasma concentrations of apoM were measured with ELISA in two SLE cohorts, all patients fulfilling ≥ 4 American College of Rheumatology (ACR) classification criteria for SLE, and 100 healthy controls (HC). In Cohort I (n= 85, 88% women, mean age 46 years), evaluation time points were selected to include a wide range of manifestations and SLEDAI scores, to assess if disease activity and certain organ involvement affect apoM levels. Cohort II was investigated cross-sectionally (n=148, 87% women, mean age 49 years) in order to measure endothelial function by EndoPAT 2000 (Itamar Medical, Israel), in relation to apoM levels. A low Reactive Hyperemia Index (RHI) value indicates endothelial dysfunction (ED). Serum-HDL and LDL were measured by routine laboratory test to analyse also these lipoproteins in relation to endothelial function. Subgroup analysis of the younger SLE patients (n=64, age 18-45 years) was performed, since the increased risk of cardiovascular disease seen in SLE is most pronounced in this patient group.

Results: In cohort I, the plasma levels of apoM were found to be significantly lower in patients with SLE (median 0.70 µM) as compared to controls (median 0.88 µM, p<0.0001). In SLE patients, the apoM concentrations correlated inversely to disease activity (SLEDAI, r= -0.29, p=0.0063) as well as to the acute phase markers CRP ( r= -0.25, p=0.0192) and sedimentation rate (r= -0.27, p=0.021). ApoM was significantly lower in patients with active nephritis, leukopenia, anti-DNA antibodies or rash compared to patients without these manifestations: median concentration in µM: 0.54 vs 0.76 p=0.0053, 0.49 vs 0.75 p=0.0042, 0.54 vs 0.76 p=0.0147 and 0.55 vs 0.79 p=0.0077, respectively . In cohort II, using linear regression analysis, there was a positive correlation between apoM levels and the RHI value in the younger SLE patients: β=0.94 CI 95% 0.22,1.65 r=0.32 p=0.011. No correlation was seen between s-HDL levels and RHI: β= -0.075 CI 95% -0.57, 0.42 r= -0.042 p=0.76. Further, we found no significant correlation between s-LDL and RHI: β=0.18 CI 95% -0.013,0.38 r= 0.25 p=0.067. 

Conclusion: SLE related inflammation has an impact by lowering plasma apoM, since high SLE disease activity was associated with low apoM levels. Hypothetically this may affect the endothelium. The lower apoM levels seen in the young SLE patients with impaired endothelial function, supports the hypothesis that apoM is important for maintaining endothelial health.    

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-plasma-concentrations-of-apolipoprotein-m-correlate-to-disease-activity-and-endothelial-dysfunction-in-sle/