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Autoantibodies against the protease inhibitor calpastatin: a new risk factor for venous thrombosis?

Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that > 90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients 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 sera (11.3%; p < 0.01 vs. blood donors, p < 0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpastatin may constitute a so far unknown risk factor for venous thrombosis.