Autoantibody selectively inhibits binding of von Willebrand factor to glycoprotein ib. Recognition site is located in the A1 loop of von Willebrand factor.
A 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34 kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first auto-antibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.
Mohri
H
H
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Yamazaki
E
E
Suzuki
Z
Z
Takano
T
T
Yokota
S
S
Okubo
T
T
D000328:Adult; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014841:von Willebrand Factor / Q000378:metabolism*
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor