Showing papers by "Otylia Kowal-Bielecka published in 2007"

Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database

Abstract: Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and Methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the ACR diagnostic criteria in participating centres. We aimed to characterize demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were female. On multivariate analysis, scleroderma subsets (dcSSc vs. lcSSc), antibody status and age at onset of Raynaud’s phenomenon, but not gender were independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis appeared more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction appeared superseded by an antibody based classification in predicting some scleroderma complications. The EUSTAR MEDS data base facilitates the analysis of clinical patterns in SSc and contributes to the standardised assessment and monitoring of SSc internationally.

Hypoxia-induced increase in the production of extracellular matrix proteins in systemic sclerosis.

Abstract: Objective Insufficient angiogenesis with tissue ischemia and accumulation of extracellular matrix are hallmarks of systemic sclerosis (SSc). Based on the severely decreased oxygen levels in the skin of patients with SSc, we aimed to investigate the role of hypoxia in the pathogenesis of SSc. Methods Subtractive hybridization was used to compare gene expression in dermal fibroblasts under hypoxic and normoxic conditions. Dermal fibroblasts were further characterized by exposure to different concentrations of oxygen and for different time periods as well as by interference with hypoxia-inducible factor 1α (HIF-1α). The systemic normobaric hypoxia model in mice was used for in vivo analyses. Results Several extracellular matrix proteins and genes involved in extracellular matrix turnover, such as thrombospondin 1, proα2(I) collagen, fibronectin 1, insulin-like growth factor binding protein 3, and transforming growth factor β–induced protein, were induced by hypoxia in SSc and healthy dermal fibroblasts. The induction of these genes was time- and dose-dependent. Experiments with HIF-1α–knockout mouse embryonic fibroblasts, deferoxamine/cobalt ions as chemical stabilizers of HIF-1α, and HIF-1α small interfering RNA consistently showed that extracellular matrix genes are induced in dermal fibroblasts by HIF-1α–dependent, as well as HIF-1α–independent, mechanisms. Using the systemic normobaric hypoxia mouse model, we demonstrated that dermal hypoxia leads to the induction of the identified extracellular matrix genes in vivo after both short exposure and prolonged exposure to hypoxia. Conclusion These data show that hypoxia contributes directly to the progression of fibrosis in patients with SSc by increasing the release of major extracellular matrix proteins. Targeting of hypoxia pathways might therefore be of therapeutic value in patients with SSc.

Mechanisms of Disease: leukotrienes and lipoxins in scleroderma lung disease--insights and potential therapeutic implications.

Abstract: Scleroderma interstitial lung disease (SLD) is a leading cause of morbidity and mortality in patients with systemic sclerosis Although the pathogenesis of SLD is not clear, excessive fibrosis and inflammatory cell infiltration are the main histologic features of this disorder Leukotrienes and lipoxins are two functionally different classes of lipoxygenase-derived eicosanoids Leukotrienes are potent proinflammatory mediators and directly and indirectly stimulate fibroblast chemotaxis, proliferation, and collagen synthesis Lipoxins counter-regulate the proinflammatory actions of leukotrienes and activate resolution of the inflammatory response In addition, lipoxins inhibit growth-factor-induced fibroblast proliferation and collagen synthesis Studies using bronchoalveolar lavage have revealed that there is an overproduction of proinflammatory and profibrotic leukotrienes in the lungs of patients with SLD, and that leukotriene levels correlate with inflammatory indices within the lungs Moreover, the increased levels of leukotrienes in these patients are not balanced by an upregulation of anti-inflammatory and antifibrotic lipoxins Unopposed actions of leukotrienes might, therefore, induce chronic inflammation and fibrosis in the lungs of SLD patients Accordingly, pharmacologic correction of a leukotriene-lipoxin imbalance using leukotriene inhibitors or lipoxin analogs might be a new approach to the treatment of SLD

[Coexistence of scleroderma-like syndrome and idiopathic myelofibrosis in a 54-year-old female patient: case report].

Abstract: Systemic sclerosis (SSc) is characterized by immunological disturbances, vascular damage and overproduction of extracellular matrix by stimulated fibroblasts. It has been postulated that immunological reactions involved in the pathogenesis of SSc may promote the development of malignancies. Coexistence of this disease with neoplasmatic processes is relatively frequent. In our report we describe a case a 54-year-old woman with scleroderma-like syndrome, which has preceded the occurrence of idiopathic myelofibrosis by many years. Owing to multiple repeated diagnostic tests we managed to diagnose this disease at the early stage, which enabled effective therapy with remission of blood dyscrasia as well as inhibition of skin lesions and lung fibrosis.