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Markers for the Factor VIII Antibody Response in Hemophilia A
Author(s) -
Shapiro S S
Publication year - 1984
Publication title -
scandinavian journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0036-553X
DOI - 10.1111/j.1600-0609.1984.tb02562.x
Subject(s) - antibody , titer , medicine , immunology , antibody titer , human leukocyte antigen , antigen
Antibodies to FVIIIC occur in 5‐5 percent of patients with hemophilia A who receive FVIII replacement therapy. Several observations suggest that the immune response to FVIIIC may be under some form of genetic control. The American Cooperative Study of FVIIIC inhibitors in hemophilia A has followed 1,522 patients with hemophilia A and has examined a number of variables relating to this problem. Antibodies were present in 216 patients at entry into the study and an additional 31 patients developed antibodies during the study. Almost all antibodies occurred in patients whose FVIIIC was < 0.03 U/ml. One quarter of the antibody patients had low‐titer antibodies despite repeated treatment, although an occasional low‐ttter antibody eventually converted to high‐titer. Among the 31 patients who developed antibodies during the study, 15 were high‐titer (>10 Bethesda U/ml) and all but 3 developed within the first 100 exposure‐days to FVIII. Studies of 167 sibships with at least 2 hemophilic brothers showed a non‐random distribution of antibodies. HLA typing of 35 antibody and 105 non‐antibody patients showed an under‐representation of HLA‐Al in antibody patients. We also studied polymorphisms of complement components C2, C4A, C4B and factor B, known to be synthesized under genetic control of loci on chromosome 6, close to the HLA‐Dr locus. The frequencies of C4A4, C4B2 and factor BF‐F were 1‐1/2 to 2 times higher in antibody formers than in non‐antibody patients. Taken together, these studies imply strongly the presence of some Immune Response gene control over the FVIIIC antibody response in patients with hemophilia A.