Functional characterization of an abnormal factor XII molecule (F XII Bern)
WA Wuillemin, I Huber, M Furlan and B Lammle
Central Hematology Laboratory, University of Bern, Switzerland.
An 18-year-old healthy woman was found to have cross-reacting material
(CRM)-positive factor XII (F XII) deficiency, F XII clotting activity was
less than 0.01 U/mL, whereas F XII antigen was 0.11 U/mL. An F XII
inhibitor was excluded. To partially characterize the molecular defect of
the abnormal F XII, immunologic and functional studies were performed on
the proposita's plasma. The abnormal F XII was a single chain molecule with
the same molecular weight (80 Kd) and the same isoelectric points (pl, 5.9
to 6.8) as normal F XII. Dextran sulfate activation of the proposita's
plasma showed no proteolytic cleavage of F XII even after 120 minutes,
whereas F XII in pooled normal plasma, diluted 1:10 with CRM-negative F
XII-deficient plasma, was completely cleaved after 40 minutes. Adsorption
to kaolin was identical for both abnormal and normal F XII. In the presence
of dextran sulfate and exogenous plasma kallikrein, the abnormal F XII was
cleaved with the same rate as normal F XII. However, kallikrein-cleaved
abnormal F XII was not able to cleave factor XI and plasma prekallikrein,
in contrast to activated normal F XII. Thus, these studies show that the
functional defect of this abnormal F XII, denoted as F XII Bern, is due to
the lack of protease activity of the kallikrein-cleaved molecule.
Therefore, the structural defect is likely to be located in the light chain
region of F XII, containing the enzymatic active site.
Volume 78,
Issue 4,
pp. 997-1004,
08/15/1991
Copyright © 1991 by The American Society of Hematology
