title: Relation of HLA-B27, tumor necrosis factor-α promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis -- a comprehensive genotype-phenotype analysis from an observational cohort.
abstract: OBJECTIVE
  In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at -308 (TNF-308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements.
  
  
  METHODS
  Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF-238, and TNF-308, and with clinical measurements.
  
  
  RESULTS
  In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF-308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms.
  
  
  CONCLUSIONS
  Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF-308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.
authors: Department of Rheumatology, Evangelische Krankenhaus Hagen-Haspe, Germany.
authors: Denis A
authors: DA
authors: Poddubnyy
authors: Elisabeth
authors: E
authors: Märker-Hermann
authors: Wiebke
authors: W
authors: Kaluza-Schilling
authors: Henning
authors: H
authors: Zeidler
authors: Jurgen
authors: J
authors: Braun
authors: Joachim
authors: J
authors: Listing
authors: Joachim
authors: J
authors: Sieper
authors: Martin
authors: M
authors: Rudwaleit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005838:Genotype; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma