@article {PODDUBNYY2436, author = {DENIS A. PODDUBNYY and ELISABETH M{\"A}RKER-HERMANN and WIEBKE KALUZA-SCHILLING and HENNING ZEIDLER and JURGEN BRAUN and JOACHIM LISTING and JOACHIM SIEPER and MARTIN RUDWALEIT}, title = {Relation of HLA-B27, Tumor Necrosis Factor-α Promoter Gene Polymorphisms, and T Cell Cytokine Production in Ankylosing Spondylitis {\textemdash} A Comprehensive Genotype-Phenotype Analysis from an Observational Cohort}, volume = {38}, number = {11}, pages = {2436--2441}, year = {2011}, doi = {10.3899/jrheum.110130}, publisher = {The Journal of Rheumatology}, 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 {\textendash}308 (TNF{\textendash}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{\textendash}238, and TNF{\textendash}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{\textendash}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{\textendash}308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/38/11/2436}, eprint = {https://www.jrheum.org/content/38/11/2436.full.pdf}, journal = {The Journal of Rheumatology} }