Assessment of disease activity, damage and quality of life in systemic lupus erythematosus: new aspects.

Systemic lupus erythematosus (SLE) is a multisystem auto-immune disorder that results from a combination of genetic, environmental and hormonal factors. The heterogeneity of disease presentation and course in different individuals and the variability in the disease progression/fluctuations within the same patient have made finding a unifying assessment tool difficult. It is currently accepted that assessment of patients with SLE cannot be accomplished with a single index. Formal evaluation of three aspects of the disease, disease activity, disease damage and patient-related quality of life (QoL), is required. In the recent decade, the pathogenesis of SLE at the cellular and molecular levels has been the subject of much research. Robust assessment tools are needed to correlate the presence of various serological markers with disease activity. In addition, multiple clinical trials of new therapies have necessitated validated measures that can give a sensitive response index. This review focusses on the SLE assessment tools currently in use and their translational application in clinical research and trials.

Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis.

Systemic sclerosis (SSc) is a disorder of systemic and dermal fibrosis of uncertain etiology. Recently, we found that SSc epidermis is abnormal, taking on an activated phenotype observed during wound healing and tissue repair. As epithelial-fibroblast interactions are important during wound repair and in fibrosis in general, we investigated further the phenotype of the SSc epidermis, and tested whether the SSc epidermis provides a pro-fibrotic stimulus to fibroblasts. In this study we show that in SSc epidermis keratinocyte maturation is delayed, and wound-associated keratins 6 and 16 are induced, in both involved and clinically uninvolved skin. Phosphorylation array analysis revealed induction of stress-induced mitogen-activated protein kinase signaling and mesenchymal feedback through hepatocyte growth factor/c-Met in SSc epidermis. SSc epidermal cells maintained with normal fibroblasts in three-dimensional co-culture were found to stimulate fibroblasts, leading to contractility and connective tissue growth factor expression. These effects depend on elevation of IL-1alpha by the epidermal cells and induction of endothelin-1 and transforming growth factor-beta in fibroblasts. Antagonism of endogenous IL-1alpha using IL-1 receptor antagonist blocked gel contraction by SSc epidermis. We propose that in SSc, epidermal cells are in a persistently activated state and are able to promote dermal fibrosis. These findings are important because biologic therapies could target epithelial-fibroblast interactions in the disease.