Oxidized Phospholipids, Lipoprotein (a) and Glycosphingolipid Associated B- 1,4 Galactosyltransferase in a Johns Hopkins cohort of patients with Systemic Lupus Erythematosus.

Background/Purpose: Systemic lupus erythematosus(SLE) is an autoimmune disease wherein the patient’s immune system attacks apparently healthy tissue. These patients develop atherosclerotic plaques,and have high rates of coronary events mostly in premenopausal women. Chronic inflammation, lipid oxidation, and production of reactive oxygen species may attribute to atherosclerosis in these patients but this relationship has not been tested. We have previously shown that oxidized phospholipids(Ox-PC) could activate B-1,4galactosyltransferase to generate a glycosphingolipid, lactosylceramide which in turn, produces reactive oxygen species in vascular cells implicated in cell proliferation, angiogenesis, and migration-hallmarks in the pathophysiology of atherosclerosis.

Methods: SLE patients form the Johns Hopkins University cohort were assessed for disease activity using the Physician Global Assessment, the SELDA, and organ involvement assessments (the SLICC/ACR Damage index). Further, laboratory tests were condcuted to ascertain organ damage, and cardiovascular risk factors. Hopkins institutional board approval was obtained for this study. The SLE patients serum(N=50) were 50% Caucasian and 40% African American women with mean age of 38. Control serum(N=50) was obtianed from 90% Caucasian and 10% African American women with the mean age of 38. Serum levels of Ox-PC per apoB-100particle (Ox-PC-apoB) was measured by ELISA using a murine monoclonal antibody EO6,which binds to the phosphorylcholine group of oxidized phospholipids but not to native phospholpipids. By the use of apoB antibody an equal number of apoB particles in serum were captured first and then Ox-PC level was measured. The serum levels of lipoprotein a(Lp(a) and B-1,4galactosyltransferase(B-1,4GalT-V) were also measured by ELISA using corresponding antibody raised against these antigens.

Results: We observed that there were more Ox-PC molecules per apoB protein in the serum of SLE patients as compared to control serum. This was highly statistically significant(p<0.0001). Since Lp(a) on apoB protein is the major carrier of OX-PC,it was not surprising to observe that the level of Lp(a) were also significantly increased in SLE serum (p< 0.0001). An unexpected finding was that the B-1,4GalT-V mass was also increased (p<0.0001) in SLE serum relative to control serum.

Conclusion: This study demonstrates that increased level of Ox-PC,Lp(a) and B-1,4GalT-V predict the pro-atherogenic and pro-inflammatory potential of these biomarkers in SLE.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/oxidized-phospholipidslipoproteina-and-glycosphingolipid-associated-b-14-galactosyltransferase-in-a-johns-hopkins-cohort-of-patients-with-systemic-lupus-erythematosus/