Production of the effector cytokine interleukin-17, rather than interferon-γ, is more strongly associated with autoimmune hemolytic anemia

Andrew M. Hall, Omar M. Zamzami, Natasha Whibley, Daniel P. Hampsey, Anne M. Haggart, Mark A. Vickers, Robert N. Barker

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Abstract

Background: Interleukin-17A is the signature cytokine of the Th17 subset and drives inflammatory pathology, but its relevance to autoantibody-mediated diseases is unclear. Th1 cells secreting interferon-gamma have been implicated in autoimmune hemolytic anemia, so the aim was to determine which cytokine is more closely associated with disease severity.

Design and Methods: Interferon-gamma and interleukin-17A were measured in the sera of patients with autoimmune hemolytic anemia and healthy donors, and in peripheral blood mononuclear cell cultures stimulated with autologous red blood cells, or a panel of peptides spanning red blood cell autoantigen.

Results: Serum interleukin-17A, but not interferon-gamma, was significantly raised in patients with autoimmune hemolytic anemia (P <0.001), and correlated with the degree of anemia. Interleukin-17A was also more prominent in the responses of peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia to red blood cells, and, again unlike interferon-gamma, significantly associated with more severe anemia (P <0.005). There were no interleukin-17A responses to red blood cells by peripheral blood mononuclear cells from healthy donors. Specific autoantigenic peptides were identified that elicit patients' interleukin-17A responses.

Conclusions: Interleukin-17A makes a previously unrecognized contribution to the autoimmune response in autoimmune hemolytic anemia, challenging the model that the disease is driven primarily by Th1 cells. This raises the possibility that Th17, rather than Th1, cells should be the target for therapy.
Original languageEnglish
Pages (from-to)1494-1500
Number of pages7
JournalHaematologica
Volume97
Issue number10
Early online date14 Mar 2012
DOIs
Publication statusPublished - 1 Oct 2012

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Keywords

  • red cells
  • autoimmune hemolytic anemia
  • autoimmunity
  • helper T cells
  • Th17
  • interferon-gamma
  • interleukin-17
  • T-lymphocyte

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