| A shift towards a T cell cytokine deficiency along with an anti-inflammatory/regulatory microenvironment may enable the synthesis of anti-FVIII inhibitors in haemophilia A patients. | |
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MedLine Citation:
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PMID: 20846164 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Despite the clinical relevance of anti-factor VIII (FVIII) antibodies (anti-FVIII inhibitors) impairing haemostatic activity of haemophilia A (HA) patients, the immunological mechanisms underlying their production are unknown. Aiming to understand more clearly the immune response in patients with [HAα-FVIII(+)] and without [HAα-FVIII(-)] anti-FVIII inhibitors, we have characterized the cytokine pattern of peripheral blood leucocytes, using an in vitro stimulation of whole blood samples with plasma-derived (pFVIII) or recombinant FVIII (rFVIII). The results highlighted decreased levels of tumour necrosis factor (TNF)-α(+) neutrophils with higher interleukin (IL)-5/TNF-α ratio in HAα-FVIII(+). All HA samples displayed decreased levels of IL-10(+) monocytes when compared to the blood donor (BD) samples. HAα-FVIII(+) showed lower levels of TNF-α(+) monocytes and increased IL-10/TNF-α ratio. Analysis of adaptive immunity revealed increased levels of interferon (IFN)-γ(+) , TNF-α(+) and IL-4(+) T-cells, from both CD4(+) and CD8(+) T cells, in HAα-FVIII(-) when compared to BD. Moreover, increased frequency of IL-10(+) B cells and higher levels of α-FVIII IgG1 were observed in HAα-FVIII(-). Basal levels of cytokine(+) B-cells, similar to BD, and higher levels of α-FVIII IgG4 are major features in HAα-FVIII(+). The global cytokine profile demonstrated a major anti-inflammatory/regulatory pattern in HAα-FVIII(+), confirmed by the in vitro stimuli with pFVIII or rFVIII. The polarized anti-inflammatory/regulatory immune response in HAα-FVIII(+) and the mixed pattern with a bias towards an inflammatory cytokine profile, modulated by IL-4 in HAα-FVIII(-), may be the key element to drive the development of distinct subclasses of anti-FVIII antibodies. These finding have implications for the design of safe and effective therapeutic protocols to control inhibitors synthesis in HA patients. |
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Authors:
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D G Chaves; C Velloso-Rodrigues; C A Oliveira; A Teixeira-Carvalho; M M Santoro; O A Martins-Filho |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-15 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 162 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-12 Completed Date: 2011-03-08 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 425-37 Citation Subset: IM |
Copyright Information:
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© 2010 Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology. |
Affiliation:
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Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. danielgcm@gmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Antibody Formation / genetics Autoantibodies / genetics, metabolism Cells, Cultured Child Cytokines / genetics, immunology, metabolism* Factor VIII / genetics, immunology, metabolism* Female Hemophilia A / blood, genetics, immunology*, therapy Humans Immunity, Innate Lymphocyte Activation Male T-Lymphocyte Subsets / immunology, metabolism*, pathology T-Lymphocytes, Regulatory / immunology, metabolism*, pathology Th1-Th2 Balance |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Cytokines; 0/F8 protein, human; 9001-27-8/Factor VIII |
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