Fw: Circulating Proteasomes

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From: " Kathi " <pureheart@...>

Sent: Monday, October 07, 2002 11:44 AM

Subject: Circulating Proteasomes

> 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.

>

> Objective. The 20S proteasome plays a leading immunologic role in the

> cytosolic generation of MHC class I restricted antigens, and it

> represents an abundant antigen in several autoimmune diseases. To

> investigate the effects of autoimmune inflammatory and perioperative

> traumatic cellular damage, we determined qualitative and quantitative

> properties of released proteasomes (circulating proteasomes,

> cProteasomes) from serum samples of patients with a variety of

> autoimmune diseases.

>

> 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 CIRCULATING PROTEASOME IMMUNE ACTIVITY AUTOIMMUNE DISEASES

>

>

>

> >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@...

>

> Submitted February 22, 2002; revision accepted April 8, 2002.

>

>

>