MOLECULAR HETEROGENEITY OF HAGEMAN TRAIT (FACTOR-XII DEFICIENCY) - EVIDENCE THAT 2 OF 49 SUBJECTS ARE CROSS-REACTING MATERIAL POSITIVE (CRM+)

  • 1 January 1979
    • journal article
    • research article
    • Vol. 94  (2) , 256-265
Abstract
Plasmas of 49 individuals with homozygous Hageman trait from 42 kindreds, all containing less than 1% of the Hageman factor (factor XII) clotting activity of pooled normal plasmas were studied. Of the plasmas, 47 contained less than 1% of Hageman factor antigen. In 2 other, unrelated individuals with Hageman trait, nonfunctional material immunologically indistinguishable from normal Hageman factor was detected in plasma by radioimmunoassay at concentrations of 39% and 80%, respectively. The plasmas did not contain circulating anticoagulants against Hageman factor and, as in ordinary Hageman trait, displayed impaired surface-mediated plasma reactions such as fibrinolysis and kinin generation. Upon immunodiffusion against anti-Hageman factor serum, these plasmas formed a single precipitin line of complete identity with normal plasma or purified Hageman factor. Upon immunoelectrophoresis, the precipitin line had the same mobility as normal Hageman factor. Nonfunctional Hageman factor and normal Hageman factor behaved identically on a Sephadex G-150 column (apparent MW = 100,000) and on sucrose density-gradient centrifugation (4.5S). Nonfunctional Hageman factor was adsorbed to kaolin as readily as normal Hageman factor, suggesting that the binding site to negatively charged surfaces is different from functional sites. Antiserum raised against Hageman factor-like material in a CRM+ [cross-reacting material positive] Hageman trait plasma specifically inactivated Hageman factor activity in normal plasma. The plasmas of 3 heterozygotes in these families contained approximately 2X as much Hageman factor antigen as Hageman factor activity, whereas those of 16 heterozygotes in ordinary (CRM-) Hageman trait families contained approximately equal amounts of activity and antigen. Homozygous Hageman trait may be CRM+ and this defect is apparently genetically determined.