The objective was to determine whether the frequency of flare in systemic lupus erythematosus (SLE) patients is increased during pregnancy and the puerperium. Seventy-eight pregnancies in 68 SLE patients attending the lupus pregnancy clinic, at St Thomas' Hospital, during the last 5 yr were included. The pregnancy period and 8 weeks post-delivery were considered. This group was compared with a control group of 50 consecutive, non-pregnant, age-matched SLE patients attending our weekly lupus clinic. Additionally, 43 of the pregnant patients carried on attending the lupus clinic for the year after puerperium, and their course was compared with themselves during pregnancy. SLE activity was assessed using the Lupus Activity Index (LAI) score. An increase ≥0.26 in the score was considered as a flare of the disease. Pregnancy and control groups were homogeneous for age, race, disease duration and distribution of autoantibodies. Sixty-five per cent of the patients flared during pregnancy and/or the puerperium and 42% flared in the control group (P = 0.015).The rates of flare per patient/month were 0.082 ± 0.004 for the pregnancy group and 0.039 ±0.003 for the control group (P < 0.001). The 43 patients whose course was controlled after the puerperium flared more frequently during pregnancy than thereafter (MCNemar test, P = 0.003). The rates of flare per patient/month were 0.093 ± 0.006 during pregnancy and the puerperium, and 0.049 ± 0.004 after the puerperium (P = 0.0015). Kidney and central nervous system involvement was not different between the pregnancy and control groups. In terms of frequency of flares, there was no difference in any of the groups between patients taking and not taking steroids. We conclude that SLE tends to flare during pregnancy. Flares are maximal during the second and third trimester and the puerperium. Flares are not more severe than in non-pregnant patients, and most of the flares can be managed conservatively. Prednisolone does not prevent flares.

Objective: To determine the prevalence of anti–high‐density lipoprotein (anti‐HDL) antibodies and to establish a possible relationship between anti‐HDL, anticardiolipin antibodies (aCL), anti–β₂‐glycoprotein I (anti‐β₂GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS).Methods: Thirty‐two patients with SLE and 36 with primary APS were enrolled in a cross‐sectional study. Twenty age‐ and sex‐matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti‐β₂GPI, and antiprothrombin antibodies and IgG anti‐HDL were measured by enzyme‐linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL₂, and HDL₃ were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence.Results: Levels of total HDL, HDL₂, and HDL₃ were reduced in patients with SLE compared with controls (mean ± SD 0.51 ± 0.3, 0.37 ± 0.3, and 0.14 ± 0.1 mmoles/liter, respectively, versus 1.42 ± 0.9, 1.01 ± 0.7, and 0.40 ± 0.2). Patients with SLE and primary APS had higher titers of anti‐HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti‐HDL titers (r = −0.48, P = 0.005) whereas in the primary APS population, IgG anti‐β₂GPI was the only independent predictor of PON activity (r = −0.483, P = 0.003). In the SLE group, anti‐HDL was inversely correlated with TAC (r = −0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02).Conclusion: IgG anti‐HDL and IgG anti‐β₂GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low‐density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.

The antiphospholipid syndrome is an autoimmune disorder characterized by increased levels of circulating antiphospholipid antibodies (aPL), increased thrombotic tendency, and pregnancy morbidity.^1,2 Although advances in the treatment and follow-up of individuals with positive aPL have markedly reduced the occurrence of thrombotic events, it has become increasingly recognized that accelerated atherosclerosis is an additional problem in patients with aPL, as in other rheumatic diseases.

This study evaluated whether IgG anticardiolipinantibody (aCL) titre and traditional risk factors for atherosclerosis bore any relationship to the intima media thickness (IMT) of carotid arteries of patients with idiopathic antiphospholipid antibodies (aPL). IMT was assessed by high-resolution sonography at the common carotid, carotid bifurcation and internal carotid in 42 (13 male, 29 female, mean age 31§ 10 years) aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. In the same subjects the following were measured: plasma fibrinogen (FNG), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI), homocysteine (HC), total cholesterol (CHO), triglycerides (TG), high density and low density lipoprotein (HDL and LDL), platelet numbers and aCL of IgG and IgM isotype. IMT of the internal carotid was greater in males than females (0.48±0.03 vs 0.39±0.01 mm, P = 0.02). IMT of the carotid bifurcation was greater in thrombotic than nonthrombotic subjects (0.50§ 0.02 vs 0.42§ 0.02 mm, P = 0.04). By simple regression, IMT of the common carotids correlated with age (P < 0.0001) IgG aCL titre (P = 0.001), FNG (P = 0.006), LDL (0.01), CHO (0.02) and PAI (P = 0.02). IMT of the carotid bifurcation correlated with age (P = 0.002), IgG aCL titre (P = 0.0002), FNG (P = 0.0001), HC (P = 0.009), CHO (P = 0.02), vWF (P = 0.01) and number of thrombotic events (P = 0.03). IMT of the internal carotids correlated with age (P = 0.002), IgG aCL titre (P = 0.0001), FNG (P = 0.0008), PAI (P = 0.002) and HC (P = 0.01). By stepwise multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (P always < 0.005). In addition, plasma FNG and HC also resulted independent predictors of IMT at the carotid bifurcation (P = 0.001 and P < 0.0001, respectively) and internal carotid (P = 0.03 and P < 0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL. Measurement of plasma HC and FNG may help define aPL subjects at higher vascular risk who may require lowering of HC and FNG by vitamin and/or pharmacologic intervention. Lupus (2002) 11, 208–214.

OBJECTIVE: To evaluate the occurrence and clinical significance of lipid peroxidation (oxidative stress) in rheumatic diseases characterized by vascular involvement. PATIENTS AND METHODS: Plasma 8-epi-PGF2alpha (oxidative stress marker) was measured by gas chromatography-mass spectrometry in 36 patients with systemic lupus erythematosus (SLE), 13 with systemic sclerosis (SSc), 13 with systemic vasculitis [Wegener's granulomatosis (WG), n = 4; Churg Strauss syndrome (CSS), n = 3; Behcet syndrome, n = 6], 12 with rheumatoid arthritis (RA) and in 23 healthy controls (n = 23). RESULTS: 8-epi-PGF2alpha levels were higher in patients with SLE (P = 0.007), SSc (P < 0.001) and vasculitis (P = 0.001) than in controls. In SLE, a positive Coombs' test and arterial hypertension independently predicted 8-epi-PGF2alpha concentrations (P = 0.004 and P = 0.001, respectively). SLE patients not taking prednisolone showed higher 8-epi-PGF2alpha concentrations than SLE patients on prednisolone (P = 0.02). In the latter group, a dose response relationship was noted between 8-epi-PGF2alpha and steroid dosage (r = 0.6, P = 0.0003). In WG and CSS, 8-epi-PGF2alpha concentrations correlated with disease activity (r = 0.8, P = 0.01) and were higher than in patients with Behcet disease (P = 0.003). CONCLUSIONS: Oxidative stress may be pathogenetically relevant in some autoimmune rheumatic diseases with vascular involvement. Amelioration of some clinical manifestations of these diseases may be envisaged by targeting lipid peroxidation with dietary or pharmacological antioxidants.

Objective. To determine whether antibodies against high-density lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with the anti-atherogenic functions of high-density lipoprotein (HDL) and relate to disease activity and damage in SLE. Methods. Seventy-seven SLE patients were compared with an age- and sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG aApoA-I, soluble vascular cell and intracellular cell adhesion molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA, paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx) metabolites by the Griess reaction, and total anti-oxidant capacity (TAC) by chemiluminescence. Results. Compared with controls, SLE patients showed higher titres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P < 0.0001), lower PON activity (P < 0.0001), increased NOx (P < 0.0001), VCAM-1 (P < 0.0001) and ICAM-1 (P = 0.0008) and lower TAC (P = 0.0006). Titres of IgG aHDL positively correlated with IgG aApo A-I (r = 0.64, P < 0.0001), NOx (r = 0.32, P = 0.007), inversely correlated with PON activity (r = −0.34, P = 0.002) and TAC (r = −0.43, P = 0.0004) and were independently associated with ICAM-1 (t = 3.509, P = 0.001). IgG aApo A-I titres correlated positively with NO (r = 0.37, P = 0.007), inversely with PON activity (r = −0.31, P = 0.006), TAC (r = −0.47, P < 0.0001) and were independently associated with HDL (t = −2.747, P = 0.008) and VCAM-1 (t = 3.311, P = 0.002), the latter alongside NOx (T = 2.271, P = 0.02). Elevated titres of IgG aHDL and IgG aApo A-I and reduced PON activity related to increased disease score (BILAG) and damage index (SLICC/ACR DI). Conclusion. In SLE, IgG aHDL and aApo A-I associate with disease activity and damage and interfere with the anti-oxidant and anti-inflammatory functions of HDL favouring atherogenesis.