Autoantibodies to factor VIII.
Anti-Factor VIII (FVIII) antibodies represent a unique model to study the relationship between natural autoreactivity (natural antibodies to FVIII of healthy individuals) and disease-associated autoimmunity ('spontaneous' FVIII inhibitors of patients with anti-FVIII autoimmune disease) to a single human protein antigen. Although natural and disease-associated anti-FVIII antibodies are not readily distinguished based on the comparison of their isotypic distribution and epitope mapping, available studies of cross-reacting idiotypes suggest that FVIII inhibitors in patient's plasma encompass two populations of anti-FVIII antibodies - some antibodies result from the clonal expansion of B lymphocytes that exist previous to the treatment with FVIII and secrete anti-FVIII antibodies with properties similar to those of natural anti-FVIII antibodies present in healthy individuals, other inhibitors are produced by B cell clones that have undergone affinity-maturation and hypermutation of the V-regions of the antibodies they produce. The implications for the treatment of autoimmune patients with anti-FVIII inhibitors are discussed.
Lacroix-Desmazes
Sébastien
S
INSERM U430, Hôpital Broussais and Universite Pierre et Marie Curie, Paris, France. sebastien.lacroix@brs.ap-hop-paris.fr
Misra
Namita
N
Bayry
Jagadeesh
J
Mohanty
Dipika
D
Kaveri
Srini V
SV
Kazatchkine
Michel D
MD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005169:Factor VIII / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D005169:Factor VIII