Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.

BLyS blockade may be most beneficial if introduced early in the course of disease in young Caucasian patients presenting with renal, musculoskeletal and skin disease in an effort to reduce long-term damage.

Objective. To examine the role of 17␤-estradiol in the regulation of the autoantigen tripartite motifcontaining protein 21 (TRIM-21) in patients with systemic lupus erythematosus (SLE).Methods. Monocytes isolated from healthy control subjects and patients with SLE were stimulated with 17␤-estradiol and/or the estrogen receptor ␣ (ER␣) antagonist methyl-piperidino-pyrazole dihydrochloride. TRIM-21, ER␣, and CREM␣ expression was determined by real-time polymerase chain reaction (PCR) analysis. MatInspector software was used to identify putative binding sites within the TRIM-21 promoter. ER␣ binding to the TRIM-21 gene promoter region in monocytes was analyzed by chromatin immunoprecipitation (ChIP) assay. TRIM-21 and interferon regulatory factor 3 protein levels were analyzed by Western blotting. Conclusion. Our results demonstrate a role of estrogen in the regulation of TRIM-21 expression through an ER␣-dependent mechanism, a pathway that we observed to be overactive in SLE patients. Treatment of monocytes with an ER␣ antagonist abrogated estrogen-induced TRIM-21 expression and, as a consequence, decreased the expression of interleukin-23. These findings identify TRIM-21 as a novel ER␣-regulated gene and provide novel insights into the link between estrogen and the molecular pathogenesis of SLE. Results

Spondyloarthropathies (SpA) are a group of inflammatory arthritides classified according to common features of peripheral and spinal arthritis. The conventional anti-inflammatory and disease-modifying or slow-acting anti-rheumatic drugs do appear to be efficacious in treatment of the peripheral arthritis in a comparable fashion to seropositive rheumatoid arthritis, however, their efficacy in axial disease is unproven. This review examines new pharmacological developments in the treatment of SpA including the specific features of sacroiliitis, enthesitis and spondylitis in addition to the peripheral manifestations. The main points that are discussed are new cyclo-oxygenase (COX)-2 specific anti-inflammatories, biological therapies, such as anti-TNF compounds, and novel uses of well-known agents.