Enhanced levels of circulating proteasomes are novel complementary markers for systemic autoimmune diseases

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 38 (F 49). 1998;

Abstract: Charité Dept. Med. III1 Institute of Biochemistry MDC of Molecular Medicine Humboldt University of Berlin One of the important enzymatic machineries of the immune defense the 20S proteasome complex has been identified as a B-cell antigen in patients with autoimmune myositis and systemic lupus erythematosus. Here we investigated whether proteasomes are elevated in the circulation of patients with distinct inflammatory diseases and whether or not elevated circulating proteasomes correlate to the presence of their autoantibodies. Circulating proteasomes were determined by using two different proteasome specific monoclonal antibodies in a sandwich-ELISA. Remarkably increased levels of circulating proteasomes (above 25 to 500 ng/ml) were detected in 74 % (20/27) of patients with poly/dermatomyositis in 54 % (18/33) of patients with SLE and in 71 % (20/28) of patients with primary Sjögren's syndrome. These levels significantly exceeded those found in the circulation of patients with various solid tumors rheumatoid arthritis and healthy controls (p < 0.001). The physiologic cut off for circulating proteasomes was calculated in serum samples of 80 healthy controls to be below 25 ng/ml. The highest levels of the antigen (400 to 560 ng/ml) were determined in patients with autoimmune myositis. Follow-up analysis revealed an association of increased levels of the free antigen and anti-proteasome titer in particular serum samples of myositis and SLE patients. The enhanced levels of circulating antigen may reflect inflammatory cell damage and appear to trigger the anti-proteasome response in patients with autoimmune myositis and SLE. le

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