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Objective To identify predictors of moderate-to-severe systemic lupus erythematosus (SLE) flare in 562 patients treated with standard therapy alone in phase III belimumab trials, and to evaluate the impact of standard therapies on preventing flares. Methods Post hoc analysis assessed baseline demographics, disease activity, and biomarkers in patients with and those without flare at treatment weeks 24 and 52. Severe flare was defined by the modified SLE Flare Index (SFI) and the development of any new British Isles Lupus Assessment Group (BILAG) A domain score. Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores. Baseline characteristics associated with a ≥10% absolute difference or a ≥50% increase in flare rates were considered predictive. Results Frequencies of flares over 52 weeks according to the SFI, any new BILAG A domain score, and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7%, 23.1%, and 32.0%, respectively. Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA–SLEDAI); anti–double-stranded DNA (anti-dsDNA) positivity; proteinuria (≥0.5 gm/24 hours); BILAG renal, vasculitic, and hematologic scores; elevated C-reactive protein levels; and B lymphocyte stimulator (BLyS) levels ≥2 ng/ml. Independent predictors by multivariate analysis at week 52 were SELENA–SLEDAI and/or BILAG renal involvement and anti-dsDNA ≥200 IU/ml (on all 3 indices); SELENA–SLEDAI and/or BILAG neurologic and vasculitic involvement (on 2 indices: any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores); BLyS levels ≥2 ng/ml (on 2 indices: the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores); and low C3 level (on the SFI). Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk. Conclusion Patients who were receiving standard SLE therapy and had renal, neurologic, or vasculitic involvement, elevated anti-dsDNA or BLyS levels, or low C3 had increased risk of clinically meaningful flare over 1 year. Hydroxychloroquine use was not predictive.

There is a high incidence of thrombosis in cancer patients. Retrospective studies indicate that lupus anticoagulant (LA) antibodies can be a thrombosis risk factor in cancer. In 77 patients with different forms of cancer LA and thrombosis incidence were retrospectively evaluated. In a prospective study, with 42 lung adenocarcinoma patients, we measured plasma LA, fibrinogen, factor VIII (FVIII), and thrombosis incidence. A high frequency of LA and thrombosis were observed in both studies. In isolation LA, increased levels of FVIII and fibrinogen could not be considered good markers for the development of thrombosis.

Objective To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic, persistently antiphospholipid antibody (aPL)–positive individuals (those with positive aPL but no vascular and/or pregnancy events). Methods The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double-blind, placebo-controlled clinical trial in which asymptomatic, persistently aPL-positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo. In a separate observational and parallel study, asymptomatic, persistently aPL-positive individuals who were taking aspirin or declined randomization were followed up prospectively. Results In the APLASA study, 98 individuals were randomized to receive aspirin or placebo (mean ± SD followup period 2.30 ± 0.95 years), of whom 48 received aspirin and 50 received placebo. In the observational study, 74 nonrandomized individuals were followed up prospectively (mean ± SD followup period 2.46 ± 0.76 years); 61 received aspirin and 13 did not. In the APLASA study, the acute thrombosis incidence rates were 2.75 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for the placebo-treated subjects (hazard ratio 1.04, 95% confidence interval 0.69–1.56) (P = 0.83). Similarly, in the observational study, the acute thrombosis incidence rates were 2.70 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for those not treated with aspirin. All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and/or systemic autoimmune disease at the time of thrombosis. Conclusion Our results suggest that asymptomatic, persistently aPL-positive individuals do not benefit from low-dose aspirin for primary thrombosis prophylaxis, have a low overall annual incidence rate of acute thrombosis, and develop vascular events when additional thrombosis risk factors are present.

In order to verify the cholesterol influence in RA severity in DBA/1J mice, we quantified the cholesterol present in the knee joints of normal (N) and with collagen II induced arthritis (CIA). Forty male DBA/1J mice, were divided in normal (n=20) and CIA group (n=20). Mice in CIA group were injected with 100 microg of collagen II emulsified in Freund's complete adjuvant. Sixteen DBA/1J (8 N and 8 CIA) received an injection of 2.96 x 10(6) Bq of (3)H-cholesterol and were anesthetized and sacrificed. Semi-fine sections were covered with LM-1 emulsion, exposed for six weeks and developed. Collagen induced edema, erythema and dysfunction of knee joints in CIA group. Radioactive cholesterol was located more on the synovial membrane, where we found the greatest density of silver grains, significantly (P

Objective To determine and compare the expression of cathepsins K and S proteins in joints with rheumatoid arthritis (RA) and osteoarthritis (OA) and to determine the effect of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) on the expression of cathepsin K in fibroblast-like synoviocytes. Method Expression and localization of cathepsins K and S were determined by immunohistochemistry in the synovium of 10 RA- and 8 OA-affected joints. Northern and Western blot analyses were performed to analyze cathepsin K and S expression in primary fibroblast-like synoviocyte cultures from RA and OA patients. The effect of IL-1 beta and TNF alpha on the expression and secretion of cathepsin K in primary cultures of synoviocytes was determined by real-time polymerase chain reaction and Western blot analysis. Staining of in situ activity was used to identify active cathepsin K enzyme in primary synovial fibroblast cultures. Results Cathepsin K and S protein expression was identified in the synovium from patients with RA and OA. Cathepsin K protein was localized in synovial fibroblasts, stromal multinucleated giant cells, and, to a lesser degree, in CD68+ macrophage-like synoviocytes. Of note is the expression of cathepsin K in synovial fibroblasts and mononuclear macrophage-like cells at sites of cartilage erosion in RA and in interdigitating cells of lymphocyte-rich areas. In contrast, cathepsin S expression was restricted to CD68+ macrophage-like synoviocytes, interdigitating cells, and endothelial cells of blood vessels. Cathepsin K protein expression in the interstitial areas and perivascular regions of RA-derived synovial specimens was 2-5 times higher than in OA samples (P Conclusion The presence of cathepsin K polypeptide in synovial fibroblasts and macrophage-like cells in normal, OA, and RA synovia suggests a constitutive expression of this protease and a role in synovial remodeling. The comparable increase in cathepsin K expression after stimulation of RA- and OA-derived synovial fibroblasts with IL-1 beta and TNF alpha further suggests that the expression of cathepsin K is independent of cellular alterations leading to the invasive phenotype of RA-synovial fibroblasts. However, the overexpression of cathepsin K in RA synovia due to an increase in the number of cathepsin K-expressing cells identifies this enzyme as a candidate protease for the pathologic degradation of articular cartilage. Cathepsin S expression in macrophage-like synoviocytes suggests dual activity in antigen presentation and matrix degradation in the inflamed synovia.

The scientific articles published in Arthritis & Rheumatism (AR reduced page charges for those countries with unfavorable exchange rates would be desirable. The actual relevance of AR that makes the relative cost of subscriptions to practice income is high. Moreover, dues for international members do not include the printed version of AR Eduardo Borba, Eloisa Bonfa: Universidade de Sao Paulo, Sao Paulo, Brazil. Address correspondence to Roger A. Levy, Blvd. 28 de setembro 77 sala 333, Vila Isabel, Rio de Janeiro, 22550 Brazil. E-mail: roger.a.levy@gmail.com. Submitted for publication September 7, 2007; accepted September 7, 2007.