title: Production of the effector cytokine interleukin-17, rather than interferon-γ, is more strongly associated with autoimmune hemolytic anemia.
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-γ have been implicated in autoimmune hemolytic anemia, so the aim was to determine which cytokine is more closely associated with disease severity.
  
  
  METHODS
  Interferon-γ 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-γ, 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-γ, 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.
authors.affiliation: Section of Immunology & Infection, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. a.m.hall@abdn.ac.uk
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hall
authors.forename: Omar M
authors.initials: OM
authors.lastname: Zamzami
authors.forename: Natasha
authors.initials: N
authors.lastname: Whibley
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Hampsey
authors.forename: Anne M
authors.initials: AM
authors.lastname: Haggart
authors.forename: Mark A
authors.initials: MA
authors.lastname: Vickers
authors.forename: Robert N
authors.initials: RN
authors.lastname: Barker
mesh_terms: D000328:Adult; D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D004198:Disease Susceptibility / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000939:Epitopes; D020381:Interleukin-17; D007371:Interferon-gamma