Autoantibody to factor VIII that has less reactivity to factor Vlll/von Willebrand Factor Complex

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Abstract
To determine the difference in reactivity of factor Vlll (FVIII) inhibitor to FVlll/von Willebrand Factor (vWF) complex and FVlll free of vWF, an autoantibody to FVlll light chain was tested. A patient (1‐3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (1‐3 IgG) was shown to be the C2 domain of FVlll light chain (2170‐2332) by Western blotting using recombinant FVlll deletions expressed in Escherichia coli. The inhibitory effect on FVlll procoagulant activity (VIII :C) of 1‐3 lgG was tested against a conventional FVlll concentrate; Haemate P, a monoclonal antibody‐purified FVlll concentrate; Hemofil M, and a recombinant FVlll (rFVIII); Kogenate. 1‐3 lgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mglgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the 1‐3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVlll by forming a complex with vWF. from 22 BU/mglgG to o.5 BU/mgIgG. Fab from the 1‐3 IgG had the same effect. In addition, vWF showed a protective effect on FVlll inactivation by the 1‐3 IgG in a dose dependent manner. Fifty‐nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with 1‐3 lgG. These results suggested that vWF could compete with the 1‐3 IgG for binding to FVIII.

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