Longitudinal profiling of anti-factor VIII antibodies in Japanese patients with congenital hemophilia A during factor VIII replacement and immune-tolerance induction therapy.
Factor VIII inhibitor
Hemophilia A
IgG subclass
Immune-tolerance induction
Journal
International journal of hematology
ISSN: 1865-3774
Titre abrégé: Int J Hematol
Pays: Japan
ID NLM: 9111627
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
09
02
2022
accepted:
14
04
2022
revised:
14
04
2022
pubmed:
4
5
2022
medline:
24
8
2022
entrez:
3
5
2022
Statut:
ppublish
Résumé
When patients with hemophilia A develop factor VIII (FVIII) inhibitors, FVIII replacement therapy becomes ineffective. Although immune-tolerance induction (ITI) therapy has been used to eradicate inhibitors, treatment is unsuccessful in approximately 30% of cases. However, the mechanism behind treatment failure remains unclarified. We retrospectively examined the longitudinal profiles of immunoglobulin G (IgG) subclasses and/or the inhibitory activities of FVIII in plasma samples from 14 Japanese patients with congenital hemophilia A during hemostatic, FVIII replacement, and/or ITI therapies. In five patients, an increase in IgG4 was observed simultaneously with a decrease in IgG1 when the patient had a history of relatively high FVIII inhibitor titers, reflecting an apparent change in humoral immunity. In addition, we examined the reactivity and specificity of the patients' anti-FVIII IgG1 and IgG4 to FVIII domains by immunoblotting. Under our experimental conditions, plasma from three patients with historically higher inhibitor titers appeared to have high titers of antibodies against the A2-a2 domain, which did not necessarily correlate with ITI failure. These observations may improve scientific understanding of the immune response to infused FVIII in patients with hemophilia A.
Identifiants
pubmed: 35503593
doi: 10.1007/s12185-022-03359-z
pii: 10.1007/s12185-022-03359-z
doi:
Substances chimiques
Hemostatics
0
Immunoglobulin G
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
423-433Subventions
Organisme : Japan Society for the Promotion of Science
ID : Grant No. 18K07885
Organisme : Japan Society for the Promotion of Science
ID : 21K07804
Organisme : Sanofi
ID : Collaborative Research Agreement
Informations de copyright
© 2022. Japanese Society of Hematology.
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