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

J Rheumatol. 2011 Nov;38(11):2436-41. doi: 10.3899/jrheum.110130. Epub 2011 Sep 1.

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cohort Studies
  • Cytokines / metabolism*
  • Female
  • Genotype
  • HLA-B27 Antigen / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / metabolism*
  • Spondylitis, Ankylosing / pathology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Cytokines
  • HLA-B27 Antigen
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma