Age determines response to anti-TNFα treatment in patients with ankylosing spondylitis and is related to TNFα-producing CD8 cells

Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TNF) alpha inhibitors in ankylosing spondylitis (AS) patients; therefore, the aim of the study was to determine age-related differences in cellular functions, which can predict the response. High disease activity AS patients were treated with TNF alpha inhibitors for 12 weeks. Based on the percentage of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement, patients were divided into responding or non-responding groups. Cytometric and clinical assessment were determined at baseline, 4, and 12 weeks after initiation of anti-TNF alpha treatment. Expression of activation markers on T cells and intracellular cytokine staining was performed. Baseline percentage of TNF alpha-producing CD8 cells was lower in responders than in non-responders (20.8 +/- 2.9 vs 40.7 +/- 8.2; P = 0.04 in T test) and increased in the responding group during the first month of treatment (20.8 +/- 2.9 vs 30.3 +/- 2.5; P = 0.02). Moreover, its baseline level correlated with age (r = 0.7; P = 0.0009) but not with BASDAI improvement adjusted for age. There were no differences in the baseline percentage of IL-4, IL-17A, and IFN gamma within CD4 and CD8 cells nor in the expression of CD25, CD28, and CD69 on these cells between responders and non-responders. However, baseline level of CD4+CD28null cells correlated with the percentage of BASDAI improvement while analysed as a continuous variable adjusted for age (r = - 0.4; P = 0.048). Clinical predictors of response were also determined. Influence of age on the response to anti-TNF alpha treatment in AS patients could be mediated by TNF alpha-producing CD8 cells.