Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3435-3441
Antibodies to the FVIII light chain that neutralize FVIII
procoagulant activity are present in plasma of nonresponder
patients with severe hemophilia A and in normal polyclonal human
IgG
Alexandre Moreau,
Sébastien Lacroix-Desmazes,
Natalie Stieltjes,
Evgueni Saenko,
Srini V. Kaveri,
Roseline D'Oiron,
Yvette Sultan,
Dorothea Scandella, and
Michel D. Kazatchkine
From INSERM U 430 and Université Pierre et Marie Curie,
Hôpital Broussais, Paris, France; Centre des Hémophiles,
Hôpital Cochin, Paris, France; Holland Laboratory, American Red
Cross, Rockville, MD; and Centre de Traitement des hémophiles,
Hôpital Bicêtre, Le Kremlin-Bicêtre,
France.
We have analyzed the properties of anti-factor VIII (FVIII)
immunoglobulin (Ig) G recovered by affinity chromatography on FVIII-Sepharose from the IgG fraction of the plasma of healthy individuals and nonresponder patients with hemophilia A. Affinity-purified anti-FVIII antibodies were found to neutralize FVIII
activity and to bind to FVIII with an affinity similar to that of
anti-FVIII IgG that had been affinity-purified from the plasma of
inhibitor-positive hemophilia patients and of patients with anti-FVIII
autoimmune disease. The antibodies also exhibited patterns of
reactivity with thrombin-digested FVIII similar to those of FVIII
inhibitors and preferentially recognized epitopes located in the light
chain of FVIII. These observations suggest that FVIII inhibitors
occurring in hemophilia A and in patients with anti-FVIII autoimmune
disease originate from the expansion of preexisting natural anti-FVIII clones that exhibit FVIII-neutralizing properties.
