TY - JOUR T1 - 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 JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.110130 SP - jrheum.110130 AU - Denis A. Poddubnyy AU - Elisabeth Märker-Hermann AU - Wiebke Kaluza-Schilling AU - Henning Zeidler AU - Jurgen Braun AU - Joachim Listing AU - Joachim Sieper AU - Martin Rudwaleit Y1 - 2011/09/01 UR - http://www.jrheum.org/content/early/2011/08/30/jrheum.110130.abstract N2 - 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. ER -