Background Anti-TNFα agents have revolutionised treatment of rheumatoid arthritis (RA), although a significant proportion of patients respond inadequately. Studies in murine and human arthritis have paradoxically shown that anti-TNF treatment can increase circulating Th17 cells but the relationship of these changes to treatment responses remains unclear.
Objectives To investigate immune correlates of anti-TNF treatment response or failure in RA patients we conducted a longitudinal study using serial clinical, ultrasound and T cells immunological assessments.
Methods 25 RA patients naïve to biological therapy were followed at 4 predetermined protocol visits during the first 12 weeks of anti-TNF treatment (etanercept or adalimumab). Improvement in Disease Activity Score of 28 joints (DAS28) defined treatment responders (n=16) and non-responders (n=9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by 2D high frequency grey scale and power Doppler ultrasound (PDUS) using a digitalised pixel counter. Changes in the frequency of circulating Th17 cells during treatment were evaluated by IL17 ELISpot assay and Flow Cytometry (FACS) of PBMCs.
Results ELISpot analysis demonstrated a significant increase in circulating IL17-producing cells 12 weeks after anti-TNFα initiation (baseline mean ± SD 466±277 vs 12 weeks mean ± SD 759±510 spSFC/106, p=0.003). FACS analysis confirmed a significant increase in CD4+IL17+ cells at treatment week 12 (baseline mean ± SD 0.7±0.5% vs 12 weeks mean ± SD 1.1±0.5%; p=0.01). This increase in circulating Th17 cells during anti-TNFα treatment was observed in patients treated with different types of anti-TNFα agents, suggesting this may be a class effect. The increase in circulating Th17 cells during treatment correlated significantly with reduction in synovial vascularity (Spearman rank r= -0.68, p=0.007) and synovial thickening (Spearman rank r= -0.39; p=0.04) as determined by PDUS. Higher numbers of circulating Th17 cells at baseline were associated with poorer anti-TNFα treatment response as defined by ultrasonographic measures.
Conclusions This is the first study to link changes in circulating Th17 cells evaluated by cellular assays with resolution of ultrasonographic features of synovitis during anti-TNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints during treatment or that TNFa may play a role in the regulation of Th17 cell production, but these two hypotheses are not mutually exclusive.
Disclosure of Interest : None declared
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