Longitudinal profiling of anti-factor VIII antibodies in Japanese patients with congenital hemophilia A during factor VIII replacement and immune-tolerance induction ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-05-03

AUTHORS

Takuji Yoshimura, Shoko Furukawa, Akihisa Oda, Tomoko Matsumoto, Kana Sasai, Midori Shima, Keiji Nogami

ABSTRACT

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. More... »

PAGES

423-433

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-022-03359-z

DOI

http://dx.doi.org/10.1007/s12185-022-03359-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1147567106

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35503593


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195 schema:name Department of Pediatrics, Nara Medical University, 840 Shijo-cho, 634-0813, Kashihara, Nara, Japan
196 Tenri School of Medical Technology, Tenri, Nara, Japan
197 rdf:type schema:Organization
198 grid-institutes:grid.410814.8 schema:alternateName Department of Pediatrics, Nara Medical University, 840 Shijo-cho, 634-0813, Kashihara, Nara, Japan
199 Department of Thrombosis and Hemostasis Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan
200 The Center of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Nara, Japan
201 schema:name Department of Pediatrics, Nara Medical University, 840 Shijo-cho, 634-0813, Kashihara, Nara, Japan
202 Department of Thrombosis and Hemostasis Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan
203 The Center of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Nara, Japan
204 rdf:type schema:Organization
 




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