Identification of plasma antibody epitopes and gene abnormalities in Japanese hemophilia A patients with factor VIII inhibitor.
Eleven Japanese hemophilia A patients with anti-factor VIII (FVIII) inhibitors were studied to localize both their inhibitory antibody epitopes and their genotypes. The inhibitor epitopes were studied in nine severe hemophilia A patients by means of a scanning method using the oligopeptide panel covering the FVIII polypeptides without the B domain. The 107 15 mer-peptides were synthesized on solid-phase pins and analyzed for their reactivity with diluted patient plasma. As indicated previously, a series of peptides corresponding to the A2 and C2 domains were recognized by plasma antibodies from 2 patients and 4 patients, respectively. In contrast, all the antibodies bound to several epitopes in the A3 domain, while an epitope 1809-1821 covering the putative factor IX binding site was found in 3 patients. Southern blotting analysis showed that 8 out of 11 patients had either gene deletions or inversions of the FVIII gene, indicating a higher proportion of gross gene alterations in inhibitor-positive hemophilia A patients. However, the correlation of gene abnormality type with epitope location was not fully established.
Sugihara
T
T
Department of Internal Medicine, Hekinan City Hospital.
Takahashi
I
I
Kojima
T
T
Okamoto
Y
Y
Yamamoto
K
K
Kamiya
T
T
Matsushita
T
T
Saito
H
H
D000328:Adult; D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood; D016022:Case-Control Studies; D007446:Chromosome Inversion; D018604:Epitope Mapping; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D006467:Hemophilia A / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data
D000906:Antibodies; D005169:Factor VIII