RT Journal Article
SR Electronic
T1 Tumor Necrosis Factor–α Promoter -308/238 Polymorphism Association with Less Severe Disease in Ankylosing Spondylitis is Unrelated to Serum TNF-α and Does Not Predict TNF Inhibitor Response
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.131315
DO 10.3899/jrheum.131315
A1 Johannes C.  Nossent
A1 Sylvia Sagen-Johnsen
A1 Gunnstein Bakland
YR 2014
UL http://www.jrheum.org/content/early/2014/07/10/jrheum.131315.abstract
AB Objective Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-α contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-α gene promoter region polymorphism, serum TNF-α levels, and clinical phenotype. Methods 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-α –238 A/G and –308 A/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61). Results TNF-α –308 GA/AA genotype was present in 14% and TNF-α –238 GA/AA genotype in 1% of patients. TNF-α –308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α –238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-α 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-α (66 vs 25%, p < 0.001). TNFi treatment did not influence serum TNF-α. There was no effect of TNF-α –308/–238 or HLA-B27 genotype on serum TNF-α or subsequent initiation of TNFi. Conclusion TNF-α –238 or –308 GA/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-α is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-α promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-α at local sites of inflammation in AS than through systemic effects.