Natural antibodies to factor VIII.
Anti-factor VIII antibodies represent a unique model to study the relationship between natural autoreactivity (natural antibodies to factor VIII of healthy individuals), disease-associated autoimmunity ("spontaneous" factor VIII inhibitors of patients with anti-factor VIII autoimmune disease) and antigen-driven immune responses (immune inhibitors in multitransfused patients with hemophilia A) to a single human protein antigen. Although natural and disease-associated anti-factor VIII antibodies are not readily distinguished based on the comparison of their isotypic distribution and epitope mapping, available studies of cross-reacting idiotypes suggest that factor VIII inhibitors in patient's plasma encompass two populations of anti-factor VIII antibodies. Some antibodies result from the clonal expansion of B lymphocytes that exist before treatment with factor VIII and secrete anti-factor VIII antibodies with properties similar to those of natural anti-factor VIII 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 patients with anti-factor VIII inhibitors are discussed.
Lacroix-Desmazes
S
S
INSERM U430 and University Pierre et Marie Curie, Hôpital Broussais, Paris, France. Panoix@hbroussais.fr
Moreau
A
A
Pashov
A
A
Sooryanarayana
Stahl
D
D
Saint-Remy
J M
JM
Kaveri
S V
SV
Kazatchkine
M D
MD
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005169:Factor VIII / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology; D006801:Humans
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D005169:Factor VIII