AUTOANTIBODIES AGAINST THE PROTEASE INHIBITOR CALPASTATIN - A NEW RISK FACTOR FOR VENOUS THROMBOSIS

Autoantibodies reactive against human calpastatin were detected by scr eening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected anti phospholipid syndrome. When further sera were analyzed it could be sho wn that >90% of calpastatin autoantibodies, detected by Western blotti ng against the partial calpastatin clone, react with the C-terminal am ino acids of the protein. Therefore, an ELISA based on a synthetic pep tide containing the C-terminal 27 amino acids of calpastatin was devel oped and 205 healthy blood donors and 138 random sera from hospital pa tients were analyzed. A total of 11 sera (3.2%) were positive with no significant difference between the two groups (7/205 and 4/138). In 80 consecutive patients with a history of venous thrombosis 9 positive s era (11.3%; p < 0.01 vs. blood donors, p < 0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpa statin may constitute a so far unknown risk factor for venous thrombos is.