Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia

B. Wootla (1, 2, 3) , A. Mahendra (1, 2, 3) , J.D. Dimitrov (1, 3) , A. Friboulet (2) , A. Borel-Derlon (4) , D.N. Rao (5) , T. Uda (6) , J.Y. Borg (7) , J. Bayry (1, 3) , S.V. Kaveri (1, 3) , S. Lacroix-Desmazes (1, 3)

1 Immunopathologie et immunointervention thérapeutique
2 GEC - Génie Enzymatique et Cellulaire
3 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
4 Laboratoire d'Hématologie Biologique [CHU Caen]
5 IISc Bangalore - Indian Institute of Science [Bangalore]
6 Oita University
7 CHU Rouen

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly between the two groups of antibodies. Proline-phenylalanine-arginine-methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG in acquired hemophilia patients are different from that of inhibitor-positive hemophilia A patients.

Mots clés: Catalytic antibody; Acquired hemophilia; Hemophilia A; FVIII inhibitor; Factor VIII; PFR-MCA

Domaines: Biochimie, Biologie Moléculaire

B. Wootla, A. Mahendra, J.D. Dimitrov, A. Friboulet, A. Borel-Derlon, et al.. Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia. FEBS Letters, 2009, 583, pp.2565-2572. ⟨10.1016/j.febslet.2009.07.009⟩. ⟨hal-00409603⟩