| Author | Chaves, Daniel Gonçalves | |
| Author | Rodrigues, Cibele Velloso | |
| Author | Oliveira, Camila Andrade | |
| Author | Carvalho, Andréa Teixeira de | |
| Author | Santoro, Marcelo Matos | |
| Author | Martins Filho, Olindo Assis | |
| Access date | 2013-09-09T16:04:53Z | |
| Available date | 2013-09-09T16:04:53Z | |
| Document date | 2010 | |
| Citation | CHAVES, Daniel Gonçalves et al. 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. Clinical and Experimental Immunology, v. 162, n. 3, p. 425-437, Dec. 2010. | pt_BR |
| ISSN | 1365-2249 | |
| URI | https://www.arca.fiocruz.br/handle/icict/6859 | |
| Language | eng | pt_BR |
| Publisher | Wiley Online Library | pt_BR |
| Rights | restricted access | pt_BR |
| Title | 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 | pt_BR |
| Type | Article | |
| DOI | 10.1111/j.1365-2249.2010.04258.x | pt_BR |
| Abstract | 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 [HAa-FVIII(+)] and without [HAa-FVIII(-)] anti-FVIII inhibitors, we have characterized the cytokine pattern of peripheral blood leucocytes, using anin vitrostimulation of whole blood samples with plasma-derived (pFVIII) or recombinant FVIII (rFVIII). The results highlighted decreased levels of tumour necrosis factor (TNF)-a + neutrophils with higher interleukin (IL)-5/TNF-aratioinHAa-FVIII(+). All HA samples displayed decreased levels of IL-10 + monocytes when compared to the blood donor (BD) samples. HAa-FVIII(+) showed lower levels of TNF-a + monocytes and increased IL-10/TNF-a ratio. Analysis of adaptive immunity revealed increased levels of interferon (IFN)-g +, TNF-a + and IL-4 + T-cells, from both CD4 + and CD8 + T cells, in HAa-FVIII(-) when compared to BD. Moreover, increased frequency of IL-10 + B cells and higher levels ofa-FVIII IgG1 were observed in HAa-FVIII(-). Basal levels of cytokine + B-cells, similar to BD, and higher levels ofa-FVIII IgG4 are major features in HAa-FVIII(+). The global cytokine profile demonstrated a major anti-inflammatory/regulatory pattern in HAa-FVIII(+), confirmed by thein vitrostimuli with pFVIII or rFVIII. The polarized anti-inflammatory/regulatory immune response in HAa-FVIII(+) and the mixed pattern with a bias towards an inflammatory cytokine profile, modulated by IL-4 in HAa-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. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/Fundação HEMOMINAS. Laboratório de Pesquisa. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação HEMOMINAS. Laboratório de Pesquisa. Belo Horizonte, MG, Brasil /Pontifícia Universidade Católica de Minas Gerais. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil | pt_BR |
| Subject | Antibody Responses | pt_BR |
| Subject | Flow Cytometry/FACS | pt_BR |
| Subject | Haematology | pt_BR |
| Subject | Immune Regulation | pt_BR |
| Subject | Intracellular Cytokine Staining | pt_BR |
