Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Sep 2007
Interstitial lung disease associated with systemic sclerosis: what is the evidence for efficacy of cyclophosphamide?
Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) that may be responsible for severe restrictive lung disease and represents one of the two main causes of disease-related death in SSc patients. Since 1993, the beneficial effect of oral or intravenous cyclophosphamide (CYC) in the treatment of SSc-related ILD has been reported in retrospective studies, one study showing improvement of pulmonary function test scores and/or chest computed tomography at 1 year and improvement of survival at 16 months. The results of two controlled trials were recently reported. ⋯ This trial did not demonstrate significant improvement of the primary or secondary endpoints in the active treatment group versus placebo. Since with the exception of the study of Silver et al. none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD. Since only a minority of SSc patients develops severe ILD, we propose that further studies evaluating CYC should focus on the subgroup of SSc patients with worsening ILD.
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HMGB1 is a nonhistone nuclear protein that can serve as a cytokine and activate innate immunity. The translocation of this molecule from the inside to the outside of cells is a critical event in inflammation, occurring following activation of certain Toll-like receptors (TLRs) as well as during the course of apoptotic as well as necrotic cell death. Because the kinetics of HMGB1 release differs from that of a conventional cytokine, it provides a broader therapeutic window and may be an important new target of therapy for inflammatory, autoimmune, and infectious diseases.
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Ann. N. Y. Acad. Sci. · Jun 2007
ReviewGlomerular targets for autoantibodies in lupus nephritis--an apoptotic origin.
Systemic lupus erythematosus (SLE) is an autoimmune syndrome where different organs may individually or simultaneously be affected. Whether SLE is one disease entity or represents a variety of intrinsically unrelated organ manifestations is unknown. Variability of clinical presentations of SLE argues against the former. ⋯ It is believed that in situ binding of anti-dsDNA antibodies by nucleosomes is involved in organ manifestations in SLE. This review will focus on nature and origin of target structures for anti-dsDNA and antinucleosome antibodies in glomerular capillary and mesangial matrix membranes. We will particularly discuss the potential role of apoptosis and release of apoptotic chromatin in terms of their putative impact in SLE.
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Ann. N. Y. Acad. Sci. · Jun 2007
ReviewScleroderma renal crisis, still a life-threatening complication.
Scleroderma renal crisis (SRC) is a major complication in patients with systemic sclerosis (SSc). SRC occurs during the first 4 years of disease evolution in more than 75% of the cases, almost exclusively in patients with diffuse SSc. Other risk factors, including preceding corticosteroid therapy, have been associated with an increased occurrence of SRC. ⋯ Nevertheless, additional antihypertensive treatments are often needed. Quite a large proportion of patients require dialysis, although this therapy may be stopped in approximately one-third of patients. Patients remaining on dialysis after 2 years can be proposed for a renal transplantation.
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Complex regional pain syndrome (CRPS) is an etiologically unclear syndrome with the main symptoms being pain, trophic and autonomic disturbances, and functional impairment that develops after limb trauma or operation and is located at the distal site of the affected limb. Because autoantibodies against nervous system structures have been described in these patients, an autoimmune etiology of CRPS is discussed. ⋯ Using a competitive binding assay, it can be shown that at least some of the CRPS sera bind to the same neuronal epitope. Autoimmune etiology of CRPS is a new pathophysiological concept and may have severe impact on the treatment of this often chronic disease.