{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:18:13Z","timestamp":1761513493774},"reference-count":42,"publisher":"The Journal of Rheumatology","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-\u03b1 contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-\u03b1 gene promoter region polymorphism, serum TNF-\u03b1 levels, and clinical phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>We did a cross-sectional and longitudinal cohort study in TNFi-naive patients with AS (n = 335). Clinical data and biological samples were collected during a research visit with genotyping for TNF-\u03b1 \u2212238 A\/G and \u2212308 A\/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>TNF-\u03b1 \u2212308 GA\/AA genotype was present in 14% and TNF-\u03b1 \u2212238 GA\/AA genotype in 1% of patients. TNF-\u03b1 \u2212308 GA\/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-\u03b1 \u2212238 GA\/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-\u03b1 level was lower in patients with AS (151 pg\/ml) than in controls (263 pg\/ml), because more patients with AS had undetectable serum TNF-\u03b1 (66 vs 25%, p &lt; 0.001). TNFi treatment did not influence serum TNF-\u03b1. There was no effect of TNF-\u03b1 \u2212308\/\u2212238 or HLA-B27 genotype on serum TNF-\u03b1 or subsequent initiation of TNFi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>TNF-\u03b1 \u2212238 or \u2212308 GA\/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-\u03b1 is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-\u03b1 promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-\u03b1 at local sites of inflammation in AS than through systemic effects.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.131315","type":"journal-article","created":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T04:56:46Z","timestamp":1405486606000},"page":"1675-1682","source":"Crossref","is-referenced-by-count":21,"title":["Tumor Necrosis Factor\u2013\u03b1 Promoter \u2212308\/238 Polymorphism Association with Less Severe Disease in Ankylosing Spondylitis is Unrelated to Serum TNF-\u03b1 and Does Not Predict TNF Inhibitor Response"],"prefix":"10.3899","volume":"41","author":[{"given":"Johannes 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