Lupus

The objective of this study was to examine mortality rates related to cerebrovascular disease in systemic lupus erythematosus (SLE) compared to the general population. Our sample was a multisite Canadian SLE cohort (10 centres, n = 2688 patients). Deaths due to cerebrovascular disease were ascertained by vital statistics registry linkage using ICD diagnostic codes. Standardized mortality ratio (SMR, ratio of deaths observed to expected) estimates were calculated. The total SMR for death due to cerebrovascular disease was 2.0 (95% confidence interval [CI] 1.0, 3.7). When considering specific types of events, the category with the greatest increased risk was that of ill-defined cerebrovascular events (SMR 44.9, 95% CI 9.3, 131.3) and other cerebrovascular disease (SMR 8.4, 95% CI 2.3, 21.6). Deaths due to cerebral infarctions appeared to be less common than hemorrhages and other types of cerebrovascular events. Our data suggest an increase in mortality related to cerebrovascular disease in SLE patients compared to the general population. The large increase in illdefined cerebrovascular events may represent cases of cerebral vasculitis or other rare forms of nervous system disease; alternately, it may reflect diagnostic uncertainty regarding the etiology of some clinical presentations in SLE patients. The suggestion that more deaths are attributed to cerebral hemorrhage, as opposed to infarction, indicates that inherent or iatrogenic factors (eg, thrombocytopenia or anticoagulation) may be important. In view of the paucity of large-scale studies of mortality attributed to neuropsychiatric outcomes in SLE, our findings highlight the need for additional research in large SLE cohorts.

T cells from patients with systemic lupus erythematosus (SLE) have high levels of cAMP response element modulator (CREM)-α which bind to the interleukin (IL-2) promoter and limit IL-2 production. In this case-controlled study, we show that CREM-α mRNA levels were higher in T cells from patients with SLE than controls while CREB mRNA levels did not differ between the two groups. CREM-α mRNA levels did not correlate with clinical characteristics, disease activity or treatment. Nevertheless, there was a trend for patients on high doses of corticosteroids to have low levels of CREM-α mRNA. The discovery of specific non-toxic medications that block the expression of CREM-α may prove useful in reversing the aberrant T cell function in SLE.

Thirty silent lupus nephritis (SLN) patients were compared to 16 individuals bearing overt lupus nephritis (OLN). Results included: years of systemic lupus erythematosus (SLE) diagnosis were significantly earlier (4.6 ± 2.8 years) in SLN than in OLN (7.18 ± 3.61) (P < 0.05). Neurological compromise, hypertension, normocitic anemia and lymphopenia were significantly prevalent in OLN than in SLN (P < 0.05). Beside normal urinary sediment and renal function tests, the SLN group showed a moderate increase of both activity (AI) and chronicity (CI) renal pathology index when compared to highly increased AI and CI in OLN (P < 0.05). Seventy percent of SLN patients were ISN/RPS Classes I (6.6%) and II (63.3%) while 81% of OLN cases were Classes III, IV (37.5%) and V. IgG, IgA, IgM, λchain, C3 and fibrinogen immune deposits were found in 90% or over in both SLN and OLN individuals while in 60% or over, both groups also showed K chain, C1q and C4 deposits. While prevalence of ANA, anti-dsDNA and anti-C1q antibodies were similar in both groups, anti-histone, anti-RNP, CIC and CH₅₀ serum levels were significantly different in OLN versus SLN (P < 0.05). We strongly suggest that indeed SLN is the earliest stage in the natural history of lupus nephritis.

Previous studies in our laboratory showed a dose-dependent and hormone-specific increase in CD154 expression in T cells from females with systemic lupus erythematosus (SLE). This present study investigates if the estrogen-dependent increase in CD154 expression is due to stabilization of the messenger RNA. T cells from female SLE patients and controls were cultured for 18 h in serum-free medium without and with estradiol 17-β (10⁷ M). T cells were either unstimulated (resting) or were activated by further culture on anti-CD3 coated plates. Actinomycin D (25 σg/mL) was added to parallel cultures to inhibit new messenger RNA synthesis. CD154 messenger RNA stability was assessed by reverse-transcription polymerase chain amplification. Resting SLE (n = 10, P = 0.88) and normal (n = 7, P = 0.65) T cells showed no significant differences in message stability in response to estradiol. CD154 messenger RNA was also not significantly stabilized in activated SLE (n = 10, P = 0.15) or activated normal (n = 6, P = 0.077) T cells in response to estradiol. These findings indicate that the estrogen-dependent increase in CD154 in SLE T cells is not due to stability of the mRNA. These data are consistent with the postulate that estradiol stimulates CD154 transcription in SLE T cells.

The objective of this study was to investigate the possible effects of the daily stress experienced during a six-month period on the cognitive functioning of patients with systemic lupus erythematosus (SLE). For this purpose, we evaluated the daily stress of 21 patients with lupus every day for six months. Later, we carried out a neuropsychological exam that included an evaluation of attention and memory. At the same time, scores on depression and anxiety were recorded with the objective of controlling other emotional variables that might be influencing these cognitive processes. The results show that daily stress was able to predict the scores on the neuropsychological variables studied. Specifically, the daily stress experienced in the previous six months is the variable with the greatest explanatory-predictive power on the scores for delayed recall visual memory, visual fluency and attention speed. This relationship proved to be negative in all three cases (R ² corr = 0.290; t = −2.712, P < 0.014); (R ² corr = 0.318; t = −2.818, P < 0.012); (R ² corr = 0.319; t −2.906, P < 0.009), which means that the greater the daily stress, the lower the score on visual memory, fluency and total attention speed. We can state that daily stress is related to impairments in visual memory, fluency and attention in patients with SLE. This effect was not found with other emotional variables, such as depression and anxiety.

During the budding process, human immunodeficiency virus (HIV) acquires several cellular proteins from the host. Thus, antibodies against self antigens found in sera patients with autoimmune disorders may cross react with host-derived or the HIV-specific proteins gp120 and gp41 on the viral envelope and probably neutralize HIV infection. To verify this hypothesis, 88 sera from HIV negative patients suffering from systemic lupus erythematosus (SLE) and other autoimmune disorders were analysed for cross reacting antibodies against HIV-1 by Western blot and FACS analysis indicating that antibodies cross-react with epitopes expressed on HIV infected or non-infected cells. Virus capture assays revealed that HIV-1_IIIB was directly recognized by 60% of sera from patients with autoimmune disorders. Sera were also tested in HIV neutralization assays with stimulated T cells. Reduction of the viral load by patient sera correlated with their reactivity in Western blot analysis. Complement further enhanced the reduction of viral titres, although no complement-mediated lysis was observed. These data suggest a possible protective role of auto-antibodies against HIV infection in lupus patients.

Aortic valve calcification is associated with atherosclerosis in the general population. We investigated the prevalence of and associates of aortic valve calcification in systemic lupus erythematosus (SLE). One-hundred and ninety-nine SLE patients enrolled in a clinical trial had aortic valve calcification assessed by helical CT. The patients had a mean age of 44.3 = 11.4 years and were 92% female, 61% Caucasian, 34% African-American, 2% Asian and 2% Hispanic. Aortic valve calcification was present in 1.5%, whereas coronary calcium was found in 43% and carotid plaque in 17%. Among cardiovascular risk factors, hs-CRP (P = 0.0592), fibrinogen (P = 0.0507), and lipoprotein(a) (P = 0.0250), were associated with aortic valve calcification. Prednisone use (P = 0.049) and use of methotrexate (P = 0.0174) were also associated with aortic valve calcification. Aortic valve calcification was associated with antiphospholipid antibody positivity (0.0287) (lupus anticoagulant, by dilute Russell viper venom time). It was not associated with coronary calcium or carotid plaque. Aortic valve calcification, although rare in SLE, was associated with some novel cardiovascular risk factors and with a marker of hypercoagulability (lupus anticoagulant). In contrast to the general population, aortic valve calcification in SLE is not associated with subclinical measures of atherosclerosis, such as coronary calcium or carotid plaque.

Menorrhagia is common in women receiving oral anticoagulation. In healthy women, reductions of up to 90% of menstrual loss have been described with the levonorgestrel releasing intrauterine device (LNG-IUS). However there is no data about the use of LNG-IUS in women receiving oral anticoagulation and so we assessed the efficacy and safety of LNG-IUS in this setting. Patients with menorrhagia who used LNG-IUS and warfarin were contacted by post and asked to complete a questionnaire assessing the extent and duration of menstrual bleeding, quality of life and treatment satisfaction. The questionnaire was sent to 23 patients and returned by 17. The amount of bleeding was reduced with the LNG-IUS in 10 (58.8%) women; amenorrhea occurred in four (23.5%), no change in blood loss in one (5.9%) and greater blood loss in two (11.8%) patients. The number of sanitary pads used was less in 12 (70.6%) patients; same in one (5.9%) patient, more in two (11.8%) patients and two (11.8%) did not remember. Five patients (29.4%) had shorter duration of bleeding, four (23.5%) had amenorrhoea, four (23.5%) had longer periods and four (23.5%) had same duration by subjective assessment. Eight (47.1%) patients felt very satisfied, four (23.5%) felt satisfied, two (11.8%) felt dissatisfied with the treatment, one felt very dissatisfied (5.9%) and two (11.8%) did not respond to the question. This small study suggests LNG-IUS is effective in reducing the duration and amount of menstrual bleeding in women with menorrhagia associated with oral anticoagulation. We feel the use of LNG-IUS is a major advance in reducing menorrhagia in women on oral anticoagulation as the previous alternative-hysterectomy-is associated with an increased risk of thrombosis and bleeding

We report one case of pregnancy-onset severe diffuse proliferative nephritis in a patient with systemic lupus erythematosus (SLE), who was successfully treated with a combination of anti-tumour necrosis factor (TNF)-alpha, plasmapheresis and high-dose intravenous gammaglobulin. No flares were observed either in clinical symptoms or in laboratory examinations during pregnancy or after delivery. Her autoantibodies except fluorescent anti-nuclear antibodies were negative. We suggest that a combination of anti-TNF-alpha, plasmapheresis and high-dose intravenous gammaglobulin may be a safe and effective therapy for pregnant patients suffering severe lupus nephritis.

Lymphoproliferative disorders are known to complicate immunosuppressive therapy and two cases of primary lymphoma of CNS (PCNSL) have previously been described in association with mycophenolate mofetil (MMF) treatment. We report the third case of PCNSL in a patient with lupus nephropathy while on MMF treatment. PCNSL may be seen more frequently considering the increased use of MMF in immunosuppressant responsive conditions.

The presence of antiphospholipid antibodies is associated with thromboembolic events, thrombocytopenia and numerous pregnancy complications such as recurrent miscarriage, preeclampsia and HELLP syndrome. This condition is known as the antiphospholipid syndrome (APS). We describe a rare case of recurrent liver necrosis postpartum in two consecutive pregnancies of woman with systemic lupus erythematosus (SLE) and positive antiphospholipid antibodies (aPL) who underwent complete recovery.

The aim of this study was to determine the association between lupus autoantibodies and the clinical manifestations and outcome in a cohort of Puerto Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled the American College of Rheumatology classification criteria for SLE. Demographic parameters, clinical manifestations over time and damage accrual were obtained at the last study visit. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test, ANOVA, logistic regression and general lineal model analyses were used to evaluate these associations. Ninety-six percent of patients were females. The cohort had a mean age of 40.2 = 12.0 years and mean disease duration of 9.6 = 7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia, lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively associated with skin ulcerations, elevated liver enzymes, renal involvement and thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia, leukopenia and lymphopenia. No positive associations were found for anti-snRNP or anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and anti-Ro antibodies are associated with several clinical manifestations and more damage accrual in Puerto Ricans with SLE. These findings provide valuable clinical and prognostic information for this ethnic population.