title: Functional characterization of an abnormal factor XII molecule (F XII Bern).
abstract: 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.
authors.affiliation: Central Hematology Laboratory, University of Bern, Switzerland.
authors.forename: W A
authors.initials: WA
authors.lastname: Wuillemin
authors.forename: I
authors.initials: I
authors.lastname: Huber
authors.forename: M
authors.initials: M
authors.lastname: Furlan
authors.forename: B
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D000327:Adsorption; D001769:Blood; D016264:Dextran Sulfate / Q000494:pharmacology; D005172:Factor XI / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism*; D005175:Factor XII Deficiency / Q000097:blood*; D005260:Female; D006801:Humans; D007526:Isoelectric Point; D007610:Kallikreins / Q000097:blood / Q000494:pharmacology; D007616:Kaolin / Q000378:metabolism; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D011288:Prekallikrein / Q000378:metabolism
chemical_list: C070315:factor XII Bern; D007616:Kaolin; D005174:Factor XII; D005172:Factor XI; D016264:Dextran Sulfate; D011288:Prekallikrein; D007610:Kallikreins