| Factor VIII-specific B cell responses in haemophilia A patients with inhibitors. | |
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MedLine Citation:
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PMID: 20536984 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Development of inhibitory antibodies to factor VIII (FVIII) provides a major complication of replacement therapy in patients with haemophilia A. The risk of inhibitor formation is influenced by the underlying FVIII gene defect. Moreover, genetic determinants in the promoter region of IL-10 and TNFalpha have been linked to an increased risk of inhibitor development. Recent cohort-studies have provided evidence that the risk of inhibitor formation is linked to intensity of treatment. Eradication of FVIII inhibitors can be achieved by frequent infusion of high dosages of FVIII, so-called immune tolerance induction (ITI). Until now, the mechanisms involved in downmodulation of the immune response to FVIII during ITI have not been unraveled. Studies performed in an animal model for haemophilia A have suggested that elimination of FVIII-specific memory B cells by high dosages of FVIII contributes to the decline in FVIII inhibitor levels during ITI. Limited knowledge is available with respect to the development and persistence of FVIII-specific memory B cells in patients with haemophilia A. Two recent studies suggest that the frequency of peripheral FVIII-specific memory B cells in haemophilia A patients with inhibitors range from <0.01 to 0.40% of that of total IgG(+) B cells. No or very low frequencies of FVIII-specific memory B cells are observed in haemophilia A patients without inhibitors and in patients treated successfully by ITI. Possible implications of these findings are discussed in the context of currently available information on the role of antigen-specific memory B cells and long-living antibody producing plasma cells in humoral immunity. |
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Authors:
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P M W van Helden; S D Van Haren; K Fijnvandraat; H Marijke van den Berg; J Voorberg |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Haemophilia : the official journal of the World Federation of Hemophilia Volume: 16 ISSN: 1365-2516 ISO Abbreviation: Haemophilia Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-06-11 Completed Date: 2011-01-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9442916 Medline TA: Haemophilia Country: England |
Other Details:
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Languages: eng Pagination: 35-43 Citation Subset: IM |
Affiliation:
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Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory and Van Creveld Laboratory, Amsterdam, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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B-Lymphocytes
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immunology* Blood Coagulation Factor Inhibitors / metabolism Enzyme-Linked Immunosorbent Assay Factor VIII / immunology*, therapeutic use Hemophilia A / immunology*, therapy Humans Immune Tolerance* Immunologic Memory / immunology* Risk Factors |
| Chemical | |
Reg. No./Substance:
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0/Blood Coagulation Factor Inhibitors; 9001-27-8/Factor VIII |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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