Detection And Regulation Of The Subunit Proteins Of Plasma Factor XIII

Plasma factor XIII circulates as a noncovalently-associated, tetrameric zymogen (a₂b₂). The a subunit has the potential catalytic function, while the b subunit may act as a carrier protein plasma. In order to study the interactions between the two subunits, specific radioimmunoassays have been developed for each subunit. The assays are valid for measuring a and b protein concentrations in plasma and serum as well as in purified systems. The a assay detects all forms of the protein (zymogen, intermediate, enzyme). Factor XIII activity was measured by the monodansylcadaverine assay. These methods were used to correlate a and b protein concentrations with factor XIII activity in normal donors, in patients with factor XIII deficiency and their family members, and in patients with factor XIII inhibitors.

The normal plasma concentration of each of the subunits of factor XIII is about 12 μg/ml, making the concentration of the zymogen complex to be 0.15 μM. All of the b protein is recovered in serum, while a variable amount of a protein (a*) is found in serum. a protein and factor XIII activity go in parallel in normal, factor XIII deficient, and heterozygous plasma samples. Deficient patients have <1% activity and <20 ng/ml a protein. Deficient patients have about 50% of the normal plasma b concentration, and heterozygotes have 50% a and 75% b protein. In three cases of spontaneous, autoimmune inhibitors against factor XIII, there was no detectable activity and b concentration was one-half normal. Following transfusion of two factor XIII deficient patients with a subunit, activity rose immediately to the expected levels, while b rose more slowly to 20% above the preinfusion level. All of these studies indicate that the circulating level of functional a subunit exerts a positive feedback effect on the concentration of b subunit in plasma.