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Circulating Proteasomes Are Markers of Cell Damage and Immunologic Activity in Autoimmune Diseases
KARL EGERER, ULRIKE KUCKELKORN, PAUL E. RUDOLPH, JENS C. RÜCKERT, THOMAS DÖRNER, GERD-R. BURMESTER, PETER-M. KLOETZEL, and EUGEN FEIST
ABSTRACT.
Methods. cProteasomes were analyzed from serum samples of 314 patients with several systemic and organ-specific autoimmune diseases and 85 healthy controls. The concentrations of cProteasomes were determined by sandwich ELISA using a monoclonal and a polyclonal proteasome-specific antibody. Followup analyses were performed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) as well as in patients with myasthenia gravis undergoing thoracoscopic thymectomy. Results. Strongly increased levels of cProteasomes (> 1000 ng/ml) were detected in samples obtained from patients with autoimmune myositis, SLE, primary Sjögren's syndrome, RA, and autoimmune hepatitis. Significant differences were observed in the mean values of cProteasomes comparing systemic with organ-specific autoimmune diseases. Followup analyses revealed a close correlation of cProteasome with the autoimmune process as well as cellular damage. Moreover, cProteasomes were isolated in intact and native as well as in degraded or dissociated forms from the serum samples. The immuno-subunit LMP7 was found to be incorporated in the circulating protease complex. Conclusion. Levels of cProteasomes are markedly elevated in patients with systemic autoimmune diseases, apparently correlating with disease activity. The cProteasomes represent novel sensitive markers of the autoimmune inflammatory processes and/or reflect the magnitude of cellular damage. (J Rheumatol 2002;29:2045-52) Key Indexing Terms:
PROTEASOME
From the Department of Rheumatology and Clinical Immunology, the Institute of Biochemistry, and the Department of Surgery, Charité University Hospital, Humboldt University of Berlin, Berlin; and the Research Institute for the Biology of Farm Animals, Research Unit Genetics and Biometry, Dummerstorf, Germany. K. Egerer PhD, MD; T. Dörner, MD; G-R. Burmester, MD; E. Feist, MD, Department of Rheumatology and Clinical Immunology; U. Kuckelkorn, PhD; P-M. Kloetzel, PhD, Institute of Biochemistry, Charité University Hospital; P.E. Rudolph, PhD, Research Institute for the Biology of Farm Animals; J.C. Rückert, MD, Department of Surgery, Charité University Hospital. Dr. Egerer and Dr. Kuckelkorn contributed equally to this work. Address reprint requests to Dr. E. Feist, Charité University Hospital, Schumannstr. 20/21, D-10117 Berlin, Germany. E-mail: eugen.feist@charite.de Submitted February 22, 2002; revision accepted April 8, 2002. |