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Common inhibitory effects of human anti‐C2 domain inhibitor alloantibodies on factor VIII binding to von Willebrand factor
Author(s) -
Shima Midori,
Nakai Hiroaki,
Scandella Dorothea,
Tanaka Ichiro,
Sawamoto Yoshikatu,
Kamisue Seiki,
Morichika Shougo,
Murakami Tomohiko,
Yoshioka Akira
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05374.x
Subject(s) - von willebrand factor , inhibitory postsynaptic potential , medicine , immunology , chemistry , cancer research , platelet
Summary. Factor VIII (FVIII) Inhibitor alloantibodies obtained from seven severe haemophilia A patients were examined for their binding regions and their effects on FVHI binding to von Willebrand factor (vWF). Immunoblotting analysis with a panel of recombinant fragments demonstrated that the binding regions of antibodies in cases 1‐5 were contained in the C2 domain of the light chain. Antibodies from cases 1 and 2, which recognized an epitope within residues 2248‐2312, completely inhibited FVIII/ vWF binding in an FXISA (IC 50 : 5‐0 and 9‐0μg/ml, respectively). Antibodies from case 3 recognizing 2170‐2312 and case 5 recognizing 2170‐2327 also inhibited FVIII/vWF binding (IC 50 :110 and 400μg/mI, respectively). Case 4 antibodies recognizing 2218‐2307 showed barely detectable inhibition and cases 6 and 7 antibodies recognizing the 44 kD heavy chain, did not inhibit. Our results demonstrate that all anti‐C2 alloantibodies with epitopes that extend to the residue 2312 inhibit vWF binding and that an overlap of the inhibitor epitope with residues 2308‐2312 is critical for maximal inhibition of vWF binding. Prevention of FVIII/vWF binding appears to be a common property of anti‐C2 domain inhibitor alloantibodies.