Proteomic Analysis Of Serum Biomarkers For Premature Atherosclerosis In Patients With Lupus

[Objective]To analyze the clinical features of systemic lupus erythematosus (SLE) patients, todetermine the prevalence of atherosclerosis in SLE and associated the traditional andnon-traditional risk factors for AS. Finally, to identify the specific serum biomarkersand the pathogenesis of premature atherosclerosis in SLE using the proteomictechnology.[Methods]1、92SLE patients without clinical history of cardiovascular disease were collectedand retrospectively analyzed. B-mode ultrasound was used to measureintima-media thickness (IMT) and assess plaques of the carotid arteries. IMTvalues≥0.9mm were considered indicative of thickened intima, and Plaques arefocal structures encroaching into the arterial lumen of at least0.5mm or50%ofthe surrounding IMT value, or demonstrates a thickness>1.5mm. Patients withthickened intima and (or) atherosclerotic plaque were included in the AS groupand others were included in the SLE group. The traditional risk factors ofatherosclerosis as well as their association with the characteristic of lupus wereevaluated and compared between the two groups of patients.2、 Patients with AS were included in the positive group after excludinghypertension, family history of coronary artery disease (CAD), diabetes,smoking, thyroid disease, other connective tissue diseases. Then select themembers of the negative group from the SLE group and the healthy people to thehealthy control group after age and gender-matched. Three groups were the sameas the number of cases.The serum samples of the three groups was analyzed byproteomic technology. Differentially expressed spots meeting ratio>2andanova≤0.05were separated after the isoelectric focusing electrophoresis (IEF)and SDS-PAGE, then excised, digested, and analyzed by MALDI-TOF MassSpectrometry. [results]1、The average age of92patients (88women,4men) was (35±11) years. The CIMTof patients was0.4to1.7mm, and the anvergae of CIMT was (0.67±0.24) mm.Wealso found that22(23.9%) of92patients had thickened intima,3(3.26%) of themhad atherosclerotic plaque,23(25%) had thickened intima and (or) plaque.2、Compared with SLE group, we found that patients with AS were older (P=0.01)and more in postmenopausal (P=0.022) as well as a higher prevalence of women(P=0.047), hypertension (P=0.016), hyperuricemia (P=0.028), hsCRP（P=0.018）,heart damage (P=0.008), the positive of ACL IgG (P=0.018). No significantdifferences were found in the BMI、family history of CHD, smoking, diabetes,lipids, SLE duration, age at diagnosis, SLEDAI, SLICC, Kidney damage, CNSinvolved, C3, C4,cumulative dose of prednisone and the use ofimmunosuppressive agents in the two groups of patients. The10-year risk of CADscore was predictive in both groups but there was no difference between them. Inlogistic regression analysis, older age (P=0.001, OR=1.096) and hyperuricemia(P=0.01, OR=1.007) were independently related to the presence of atherosclerotic.3、Among the positive group, negative group and healthy control group included inthe proteomic anlysis, no significant differences were found in age, gender, lipidsand so on.We also could not find any significant difference in disease duration,SLEDAI-2000, SLICC, organ damage, autoantibodies, the inflammatoryindicators cumulate dose of prednisone and so on between the positive group andthe negative group. In this experiment,10of the24differentially expressedprotein spots which were observed between the three groups were excised andanalyzed by MALDI-TOF-MS. The protein spots were identified asBeta-2-glycoprotein1（β2-GP1）, Haptoglobin (HP), Haptoglobin related protein(HPR), Igα1-C chain, Igα2-C chain, Zinc-alpha-2-glycoprotein (ZAG), VitaminD-binding protein (VDBP) and complement C3.[Conclusion]1、 SLE patients have a prevalence of premature atherosclerosis. Traditional riskfactors for cardiovascular disease, SLE itself and disease related factors may all play important roles in the pathogenesis of premature atherosclerosis. The riskfactors associated with atherosclerosis in SLE patients are age andhyperuricemia.2、 β2-GP1, HP, HPR, the Igα1-C chain, Igα2-C chain, ZAG, DBP and complementC3may play an important role in the development of atherosclerosis in SLE, andthey may be the biomarkers of atherosclerosis in SLE.