Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-b 2 -glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM .2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

No abstract

No abstract

Oral tolerance induced with HSP65 could prove to be a novel means of suppressing atherogenesis.

Background-Immunization with ␤ 2 -glycoprotein I (␤2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of ␤2GPI immunization on the progression of atherosclerosis. Methods and Results-In the first experiment, 3 groups of LDL receptor-deficient (LDL-RD) mice (nϭ15 per group) were immunized with either ␤2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (nϭ10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All ␤2GPI-immunized mice developed high titers of anti-␤2GPI antibodies as well as a specific lymph node proliferation to ␤2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the ␤2GPI-immunized mice (mean aortic lesion, 26 000Ϯ5700 m 2 ) in comparison with their ovalbumin-immunized (mean, 3000Ϯ1099 m 2 ; PϽ0.01) and nonimmunized (mean, 2250Ϯ700 m 2 ; PϽ0.01) littermates. The average lesion size in the ␤2GPI-immunized mice fed an atherogenic diet (mean, 98 000Ϯ8305 m 2 ) was larger than the ovalbumin-immunized mice (mean, 81 250Ϯ12 933 m 2 ; PϭNS) or the nonimmunized controls (mean, 75 625Ϯ7281 m 2 ; PϭNS). The atherosclerotic plaques in the ␤2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. Conclusions-The results of the present study provide the first direct evidence for the proatherogenic effect of ␤2GPI immunization and establish a new model for immune-mediated atherosclerosis. (Circulation. 1998;98:1108-1115.)

Abstract-Recent data suggest that the immune system is involved in atherogenesis. Thus, interest has been raised as to the possible antigens that could serve as the initiators of the immune reaction. In the current work, we studied the effects of immunization with recombinant heat shock protein-65 (HSP-65) and HSP-65-rich Mycobacterium tuberculosis (MT) on early atherogenesis in C57BL/6J mice fed either a normal chow diet or a high-cholesterol diet (HCD). A rapid, cellular immune response to HSP-65 was evident in mice immunized with HSP-65 or with MT but not in the animals immunized with phosphate-buffered saline (PBS) alone. Early atherosclerosis was significantly enhanced in HCD-fed mice immunized with HSP-65 (nϭ10; mean aortic lesion size, 45 417Ϯ9258 m 2 ) or MT (nϭ15; 66 350Ϯ6850 m 2 ) compared with PBS-injected (nϭ10; 10 028Ϯ3599 m 2 ) or nonimmunized (nϭ10; 9500Ϯ2120 m 2 ) mice. No fatty streak lesions were observed in mice fed a chow diet regardless of the immunization protocol applied. Immunohistochemical analysis of atherosclerotic lesions from the HSP-65-and MT-immunized mice revealed infiltration of CD4 lymphocytes compared with the relatively lymphocyte-poor lesions in the PBS-treated or nonimmunized mice. Direct immunofluorescence analysis of lesions from HSP-65-and MT-immunized mice fed an HCD exhibited extensive deposits of immunoglobulins compared with the fatty streaks in the other study groups, consistent with the larger and more advanced lesions found in the former 2 groups. This model, which supports the involvement of HSP-65 in atherogenesis, furnishes a valuable tool to study the role of the immune system in atherogenesis.

No abstract

No abstract