AUTOANTIBODY INHIBITS BINDING OF VON-WILLEBRAND-FACTOR TO GLYCOPROTEIN IB AND COLLAGEN IN MULTIPLE-MYELOMA - RECOGNITION SITES PRESENT ON THE A1 LOOP AND A3 DOMAINS OF VON-WILLEBRAND-FACTOR

A 49-year-old man with multiple myeloma (IgG-lambda) Bence-Jones prote in positive) presented a bleeding tendency: characterized intramuscula r hemorrhage. Coagulation studies showed a von Willebrand factor (vWF) defect (Duke bleeding time > 20 min; ristocetin cofactor activity [vW F:RC], 6%; significant reduction of large multimers of vWF. Mixing stu dy suggested the presence of inhibitor directed against vWF:RC activit y and collagen binding activity of vWF. The inhibitor was identified a s an antibody of the IgG class. The inhibitor blocked the interaction of vWF with glycoprotein Ib in the presence of ristocetin, as did the pepsin-digested fragment of the inhibitor [F(ab)(2)'], but neither blo cked botrocetin-mediated interaction of vWF with glycoprotein Ib. They also inhibited the binding of vWF to immobilized collagen type I. The inhibitor and the F(ab)(2)' reacted strongly with native vWF and frag ment I (amino acids 911-1365) and with the 39/34 kDa fragment (amino a cids 480/481-718), but not with fragment II (amino acids 1366-2050) an d fragment III-T2 (heavy chains, amino acids 273-511; light chains, am ino acids 674-728). We conclude that the IgG antibody inhibits both vW F:RC activity and the binding of vWF to collagen by reacting with the epitopes present on the A1 loop and A3 domains of vWF. (C) 1998 Rapid Science Ltd.