Does antithrombin-resistant prothrombin Yukuhashi mutation also cause thrombomodulin resistance in fibrinogen clotting but not in protein C activation?
rTM treatment reduced the relative fibrinogen-clotting activity of the wild-type down to 8.4% in a concentration-dependent manner, whereas the activity of the mutant was only decreased to 44%. In the absence of rTM, APC generation activity (∆A/min at 405nm) was fairly low (0.0089 for the wild-type and 0.0039 for the mutant). In the presence of rTM, however, APC generation activity was enhanced to 0.0907 (10.2-fold) for the wild-type and to 0.0492 (12.6-fold) for the mutant, and the relative activity of the mutant with rTM was 54% of that of the wild-type. These data suggested that the prothrombin Yukuhashi mutation may cause TM resistance in terms of inhibition of fibrinogen clotting; this may contribute to susceptibility to thrombosis, although the enhancing effect of APC generation can be maintained.
Our results probably suggest that the serum levels of CXCL1 and CXCL9 play important roles in T1D pathogenesis. It is also worth noting that these factors are useful prognostic and/or diagnostic biological markers in T1D patients.