Sm22.6 antigen is an inhibitor to human thrombin

The physiological role of Schistosomiasis mansoni 22.6 antigen (sm22.6 Ag) and its pathogenic effect on the human host has never been reported. Recombinant sm22.6 Ag is a homogenous polymer under non-denaturing/non-reducing conditions, and an inhibitor to human thrombin. Kinetic and Western blot assays show that the recombinant protein interacts with human thrombin and inhibits proteolytic activity of the protease. Tests of whole blood revealed that coagulation time was significantly delayed (3–5 times longer) in the presence of the recombinant protein at a concentration similar to thrombin in normal blood samples. Kinetic studies revealed that the delayed coagulation time was due to the inhibition of α-thrombin proteolytic activity by the parasite protein in an irreversible pattern, and a reversible inhibition to γ-thrombin. Also, Western blot analysis under non-denaturing/non-reducing conditions showed that sm22.6 Ag binds to both α- and γ-thrombin. Our results strongly suggest that sm22.6 antigen plays a role in down-regulation of coagulation in humans.