title: Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis.
abstract: OBJECTIVE
  To identify an immunologic basis for the male sex bias in ankylosing spondylitis (AS).
  
  
  METHODS
  Cohorts of male and female patients with AS and age- and sex-matched healthy control subjects were selected, and the levels of serum cytokines (interferon-γ [IFNγ], tumor necrosis factor α, interleukin-17A [IL-17A], and IL-6) were examined by enzyme-linked immunosorbent assay, the frequencies of Th1 and Th17 cells were assessed by flow cytometry, and whole blood gene expression was analyzed using both microarray and NanoString approaches.
  
  
  RESULTS
  The frequency of IL-17A and Th17 cells, both of which are key factors in the inflammatory Th17 axis, was elevated in male patients with AS but not in female patients with AS. In contrast, AS-associated alterations in the Th1 axis, such as the frequency of IFNγ and Th1 cells in serum, were independent of a patient's sex. Results of microarray analysis supported an altered Th17 axis in male patients, with a specific increase in IL17RA. In addition, male and female patients with AS displayed shared gene expression patterns, while male patients with AS had additional alterations in gene expression that were not seen in female patients with AS. The differential sex-related immune profiles were independent of HLA-B27 status, clinical disease activity (as measured by the Bath Ankylosing Spondylitis Disease Activity Index), or treatment (with nonsteroidal antiinflammatory drugs or biologic agents), implicating intrinsic sexual dimorphism in AS.
  
  
  CONCLUSIONS
  The results of this study demonstrate distinct sexual dimorphism in the activation status of the immune system in patients with AS, particularly in the Th17 axis. This dimorphism could underlie sex-related differences in the clinical features of AS and could provide a rationale for sex-specific treatment of AS.
authors.affiliation: University of Toronto, Toronto Western Hospital, and University Health Network, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Gracey
authors.affiliation: University of Toronto, Toronto Western Hospital, and University Health Network, Toronto, Ontario, Canada.
authors.forename: YuChen
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Toronto Western Hospital and University Health Network, Toronto, Ontario, Canada.
authors.forename: Blerta
authors.initials: B
authors.lastname: Green
authors.affiliation: University of Toronto, Toronto Western Hospital, and University Health Network, Toronto, Ontario, Canada.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Qaiyum
authors.affiliation: University of Toronto, Toronto Western Hospital, and University Health Network, Toronto, Ontario, Canada.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Baglaenko
authors.affiliation: Toronto Western Hospital and University Health Network, Toronto, Ontario, Canada.
authors.forename: Aifeng
authors.initials: A
authors.lastname: Lin
authors.affiliation: Toronto Western Hospital and University Health Network, Toronto, Ontario, Canada.
authors.forename: Ammepa
authors.initials: A
authors.lastname: Anton
authors.affiliation: Toronto Western Hospital and University Health Network, Toronto, Ontario, Canada.
authors.forename: Renise
authors.initials: R
authors.lastname: Ayearst
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Yip
authors.affiliation: University of Toronto, Toronto Western Hospital, and University Health Network, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008297:Male; D046228:Microarray Analysis; D010446:Peptide Fragments / Q000097:blood; D016133:Polymerase Chain Reaction; D048348:Reverse Transcription; D012737:Sex Factors; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000473:pathology; D058504:Th17 Cells / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020381:Interleukin-17; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C069261:interferon gamma (1-39); D007371:Interferon-gamma