The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors

The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors

Hemophilia A (HA) is an X-linked inherited bleeding disorder, resulting from a qualitative or quantitative deficiency of clotting factor VIII (FVIII). Antibodies against FVIII, also called inhibitors, block the procoagulant activity of FVIII; thus, impairing hemostatic activity in patients with HA....

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Published in:BMC hematology Vol. 15; no. 1; p. 1
Main Authors: Silveira, Amanda Co, Santana, Marcio Ap, Ribeiro, Isabella G, Chaves, Daniel G, Martins-Filho, Olindo A
Format: Journal Article
Language:English
Published: England BioMed Central Ltd 16-01-2015
BioMed Central
Subjects:
Blood coagulation factor VIII
Care and treatment
Genetic aspects
Health aspects
Hemophilia
Immune response
Immunity
Medical equipment and supplies industry
Medical test kit industry
Physiological aspects
United States
Intracellular cytokine staining
FVIII inhibitors
Immune regulation
Cytokine profile
Hemophilia A
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Summary:Hemophilia A (HA) is an X-linked inherited bleeding disorder, resulting from a qualitative or quantitative deficiency of clotting factor VIII (FVIII). Antibodies against FVIII, also called inhibitors, block the procoagulant activity of FVIII; thus, impairing hemostatic activity in patients with HA. The exact mechanism underlying the immunological events behind the development of inhibitors remains unknown. This study aimed to understand immune response to FVIII in patients with HA who were either positive [HAα-FVIII(+)] or negative [HAα-FVIII(-)] for inhibitors. Cytokine profiles [interferon-γ (IFN - γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, and IL-10] of innate and adaptive immune cells present in the peripheral blood of participants were characterized. Presence of inhibitors was significantly associated with decreased frequencies of TNF-α-positive monocytes and neutrophils, IL-5-positive monocytes, IL-4-positive neutrophils, and increased frequencies of IL-10-positive neutrophils and T cells. T cells from HAα-FVIII(-) patients expressed increased levels of almost all cytokines. In contrast, HAα-FVIII(+) patients showed lower levels of all cytokines in CD4(+) and CD8(+) T cells, except IL-10. B cells from HAα-FVIII(-) patients expressed increased levels of IL-4 while those from HAα-FVIII(+) patients expressed increased levels of IL-10. The global cytokine profiles of innate and adaptive immune cells showed an anti-inflammatory/regulatory pattern in HAα-FVIII(+) patients and a mixed pattern, with a bias toward inflammatory cytokine profile, in HAα-FVIII(-) patients. The occurrence of these profiles seems to be associated with presence FVIII inhibitors.
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ISSN:2052-1839
2052-1839
DOI:10.1186/s12878-014-0019-8