Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases.
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.


CONCLUSIONS
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.
Egerer
Karl
K
Department of Rheumatology and Clinical Immunology, Institute of Biochemistry, Humboldt University of Berlin, Berlin, Germany.
Kuckelkorn
Ulrike
U
Rudolph
Paul E
PE
Rückert
Jens C
JC
Dörner
Thomas
T
Burmester
Gerd-R
GR
Kloetzel
Peter-M
PM
Feist
Eugen
E
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D003546:Cysteine Endopeptidases / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009097:Multienzyme Complexes / Q000097:blood / Q000276:immunology*; D009157:Myasthenia Gravis / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000601:surgery; D046988:Proteasome Endopeptidase Complex; D013934:Thymectomy
D015415:Biomarkers; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex