Lupus

Patients with systemic lupus erythematosus (SLE) with B-lymphocyte stimulator (BLyS) levels ≥ 2 ng/mL are at increased risk of flare. A regression analysis was undertaken to identify routine clinical measures that correlate with BLyS ≥ 2 ng/mL. Efficacy and safety of belimumab 10 mg/kg were examined in patients with BLyS ≥ 2 ng/mL and < 2 ng/mL.

Data from BLISS-52 and -76 (N = 1684) were pooled post hoc. A univariate logistic regression was employed to identify factors predictive of baseline BLyS ≥ 2 ng/mL. Factors significant at the 0.05 level then entered a stepwise logistic regression as covariates. Efficacy endpoints included SLE responder index (SRI), ≥ 4-point reduction in Safety of Estrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and risk of severe flare over 52 weeks. Adverse events (AEs) were analyzed for each treatment arm and BLyS subgroup.

Baseline predictors of BLyS ≥ 2 ng/mL included positive anti-Smith (≥ 15 U/mL), low complement (C) 3 (< 900 mg/L), anti-double-stranded DNA (anti-dsDNA) 80–200 and ≥ 200 IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP), and low total lymphocyte count for all patients. Belimumab 10 mg/kg led to significantly greater SRI responses over 52 weeks versus placebo in both BLyS subgroups, though treatment differences were numerically greater at Week 52 in the BLyS ≥ 2 ng/mL group (24.1%, p < 0.0001) compared with BLyS < 2 ng/mL (8.2%, p = 0.0158). Results were similar for ≥ 4-point reduction in SELENA-SLEDAI. Risk of severe flare over 52 weeks was significantly reduced with belimumab 10 mg/kg versus placebo in the BLyS ≥ 2 ng/mL group (p = 0.0002). AEs were similar across treatment arms and BLyS subgroups.

Positive anti-Smith, low C3, anti-dsDNA ≥ 80 IU/mL, immunosuppressant usage, proteinuria, elevated CRP, and low total lymphocyte count were predictors of BLyS ≥ 2 ng/mL. Monitoring these factors could identify patients with BLyS ≥ 2 ng/mL who are at risk of flare.

The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE).

Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL.

The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1–374.9), 172.3 (125.3–421.9), 371.3 (143–543) vs 122.1 (76.1–212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients.

TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.

To provide information about the needs of patients with systemic lupus erythematosus (SLE) using Carenity, the first European online platform for patients with chronic diseases.

At one year after its creation, all posts from the Carenity SLE community were collected and analysed. A focused cross-sectional online survey was performed.

The SLE community included 521 people (93% females; mean age: 39.8 years). Among a total of 6702 posts, 2232 were classified according to disease-related topics. The 10 most common topics were ‘lupus and …’ either ‘treatment’, ‘fatigue’, ‘entourage’, ‘sun exposure’, ‘diagnosis’, ‘autoimmune diseases’, ‘pregnancy’, ‘contraception’, ‘symptoms’ or ‘sexuality’. 112 SLE patients participated in the online survey. At the time of diagnosis, only 17 (15%) patients had heard of SLE and 84 (75%) expressed a need for more information on outcomes (27%), treatments (27%), daily life (14%), patients' associations (11%), symptoms (8%), the disease (8%) and psychosocial aspects (7%). When treatment was initiated, 48 patients (43%) would have liked more information about side effects (46%), long-term effects (21%), treatment duration/cessation (12.5%) and type (10%) and mechanism of action (8%) of treatments. All participants except one had used the internet to find information about SLE. Sources of information included healthcare providers (51%/61%/67%), journals/magazines (7%/12%/6%), lupus Websites (51%/77%/40%), web forums/blogs (34%/53%/19%), patients' associations (11%/23%/9%) accessed at ‘just before diagnosis’, ‘just after diagnosis’ and ‘before treatment initiation’.

Online patient communities provide original unbiased information that can help improve provision of information to SLE patients.

Cutaneous lupus erythematosus (CLE) may have prognostic implications for systemic lupus erythematosus (SLE). We aimed to determine the impact of discoid lupus erythematosus (DLE) and malar rash on SLE disease activity.

Data were analyzed from the Toronto Lupus Clinic prospective cohort study. We compared SLE patients with active DLE or malar rash at SLE diagnosis to SLE patients who never developed CLE. Outcomes were assessed at one and five years, including Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (AMS).

A total of 524 SLE patients (284 without CLE, 65 with DLE, and 175 with malar rash) were included. Mean AMS scores in patients without CLE at one and five years were 5.96 ± 5.06 and 4.00 ± 3.52, which did not differ significantly from scores at one (6.93 ± 5.31, p = 0.17) and five years (4.29 ± 2.62, p = 0.63) in the DLE group. In patients with malar rash, AMS scores at one (8.30 ± 6.80, p < 0.001) and five years (5.23 ± 3.06, p = 0.004) were higher than controls without CLE.

Malar rash may be a marker of more severe systemic disease over time, while DLE has no significant impact on general SLE disease activity.

Using a population-based cohort study, we investigated whether sleep disorders (SDs) increase the risk of systemic lupus erythematosus (SLE).

We identified patients with SDs and a control cohort from 1998–2001 by using the Taiwan Longitudinal Health Insurance Database 2000. Two controls for each patient with an SD were selected and randomly frequency-matched according to age, gender, and index year. The follow-up person–years were estimated for the patients from the index date to SLE diagnosis, loss to follow-up, or the end of 31 December 2011. We used the Cox proportional hazards models to evaluate how SDs influence the risk of SLE after adjustments for demographic factors and comorbidities.

A total of 144,396 subjects (48,132 SD cases and 96,264 controls) were followed for 1,477,055 person–years. The patients with SDs displayed higher incidence density rate of developing SLE than did the controls (1.03 vs 0.46 per 10,000 person–years). After adjustment for covariates, the patients with SDs exhibited a 2.20-fold higher adjusted hazard ratio (aHR) of developing SLE than the controls (95% confidence interval (CI) = 1.44–3.36). Women exhibited a greater prevalence of SDs and SLE compared to men. Patients with SDs aged 49 years and younger exhibited a significantly increased risk of SLE compared to the controls (aHR=2.30, 95% CI = 1.33–3.98). Patients with SDs living in urban areas exhibited a significantly increased risk of SLE.

This large population-based cohort study revealed that SDs increase the risk of SLE development.

We investigated whether primary antiphospholipid syndrome (PAPS) is characterized by a deficiency in immunoregulatory pathways, a phenomenon recently implicated in the pathogenesis of autoimmune diseases.

Serum levels of immunoregulatory (e.g. IL-10 and TGF-β₁) and proinflammatory (e.g. IL-17A) cytokines were measured in PAPS, systemic lupus erythematosus (SLE) with secondary APS (SAPS), or without APS, and in healthy controls (n = 40 in each group). In a subgroup of PAPS patients we also compared phenotype and function (flow cytometry) of regulatory T-cells (Treg) and cytokine production by effector T-cells.

Our major finding was decreased levels of TGF-β₁ in PAPS and SAPS as compared to SLE without APS and controls. TGF-β₁ was the lowest in PAPS patients showing high levels of aPL IgG with significant negative correlation with the titer. SLE patients were characterized by lower serum levels of IL-2 and increased IL-17A, as compared to the other groups. The numbers of circulating Treg cells and their phenotype (e.g. FoxP3 isoforms) were not disturbed in PAPS. However, surface expression of latency associated peptide (binds TGF-β) in activated FoxP3 + cells and in vitro production of TGF-β₁ were decreased in PAPS patients with high titers of aPL IgG. Moreover, frequencies of cytokine producing effector T-helper cells (including Th17) were significantly elevated in this group.

PAPS patients with high titers of aPL IgG antibodies were characterized by decreased systemic levels of TGF-β₁ and its impaired production in vitro, suggesting impaired immunoregulation and enhanced adaptive autoimmune responses leading to the production of aPL antibodies.

B factor (BF) from the alternative complement pathway seems to participate in the pathophysiology of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

To study the allotypic variability of BF in SLE and their associations with clinical and autoantibodies profile.

BF allotypes were determined by high-voltage agarose gel electrophoresis, under constant cooling, followed by immunofixation with anti-human BF antibody, in 188 SLE patients and 103 controls. Clinical and serological data were obtained from medical examination and records.

No significant differences of BF variants between patients and controls were found, neither in relation to epidemiologic or clinical manifestations. Associations of phenotype BF SS07 and allotype BF*S07 were found with anticardiolipin IgM (aCl-IgM) antibodies (p = 0.014 and p = 0.009 respectively), but not with aCl-IgG, lupus anticoagulant (LA), anti β2GPI or clinical APS. A significant decrease in BF*F allotype (p = 0.043) and BF SF phenotype (p = 0.018) was detected in patients with anti-phospholipid antibodies as a whole (aCl-IgG, aCl-IgM, LA and anti β2GPI).

There is a link between phenotype BF SS07 and allotype BF*S07 with aCl-IgM in SLE patients; BF*F allotype could be considered a marker of protection against the development of antiphospholipid antibodies in these patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries.

To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy.

Women aged 18–40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L.

Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95%CI 1.96–147.72, p = 0.01).

From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients.