Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis
Background<br/> Anti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment, however a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating Th17 cells, but the re...
| Main Authors: | , , , , , |
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| Format: | Journal article |
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BioMed Central
2016
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| _version_ | 1797069823663931392 |
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| author | Hull, D Cooksley, H Chokshi, S Williams, R Abraham, S Taylor, P |
| author_facet | Hull, D Cooksley, H Chokshi, S Williams, R Abraham, S Taylor, P |
| author_sort | Hull, D |
| collection | OXFORD |
| description | Background<br/> Anti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment, however a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating Th17 cells, but the relationship to treatment response is unclear. To identify immune correlates of anti-TNF treatment response, we conducted a longitudinal study using clinical, ultrasound and T-cell assessments. <br/><br/> Methods <br/> 25 RA patients were studied at protocol visits during the initial 12 weeks of antiTNF treatment. Improvement in DAS28 score >1.2 defined treatment responders (n=16) and non-responders (n=9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by grey scale and power Doppler ultrasound. The frequency of circulating Th17 cells was determined by IL17 Elispot and Flow Cytometry (FACS). <br/><br/> Results <br/> The frequency of circulating IL17-producing cells increased significantly 12 weeks after anti-TNF initiation (Elispot median (range) spSFC/106 360 (280-645) vs 632 (367- 1167), p=0.003). The increase in CD4+IL17+ cells at 12 weeks was confirmed by FACS (median (range) %, 0.7 (0.5-0.9) vs 1.05 (0.6-1.3); p=0.01). The increase in circulating Th17 cells inversely correlated with reduction in synovial vascularity (r=-0.68, p=0.007) and thickening (r=-0.39; p=0.04). Higher frequencies of circulating Th17 cells at baseline were associated with poorer anti-TNF treatment response defined by ultrasonographic measures. <br/><br/> Conclusions <br/> These results demonstrate a link between changes in circulating Th17 cells with resolution of ultrasonographic features of synovial inflammation and vascularity during antiTNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints or TNF-driven regulation of Th17 cell production. |
| first_indexed | 2024-03-06T22:30:09Z |
| format | Journal article |
| id | oxford-uuid:58048d5c-5b23-460c-979d-a3e5bdf769c5 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:30:09Z |
| publishDate | 2016 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:58048d5c-5b23-460c-979d-a3e5bdf769c52022-03-26T17:00:21ZIncrease in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:58048d5c-5b23-460c-979d-a3e5bdf769c5Symplectic Elements at OxfordBioMed Central2016Hull, DCooksley, HChokshi, SWilliams, RAbraham, STaylor, PBackground<br/> Anti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment, however a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating Th17 cells, but the relationship to treatment response is unclear. To identify immune correlates of anti-TNF treatment response, we conducted a longitudinal study using clinical, ultrasound and T-cell assessments. <br/><br/> Methods <br/> 25 RA patients were studied at protocol visits during the initial 12 weeks of antiTNF treatment. Improvement in DAS28 score >1.2 defined treatment responders (n=16) and non-responders (n=9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by grey scale and power Doppler ultrasound. The frequency of circulating Th17 cells was determined by IL17 Elispot and Flow Cytometry (FACS). <br/><br/> Results <br/> The frequency of circulating IL17-producing cells increased significantly 12 weeks after anti-TNF initiation (Elispot median (range) spSFC/106 360 (280-645) vs 632 (367- 1167), p=0.003). The increase in CD4+IL17+ cells at 12 weeks was confirmed by FACS (median (range) %, 0.7 (0.5-0.9) vs 1.05 (0.6-1.3); p=0.01). The increase in circulating Th17 cells inversely correlated with reduction in synovial vascularity (r=-0.68, p=0.007) and thickening (r=-0.39; p=0.04). Higher frequencies of circulating Th17 cells at baseline were associated with poorer anti-TNF treatment response defined by ultrasonographic measures. <br/><br/> Conclusions <br/> These results demonstrate a link between changes in circulating Th17 cells with resolution of ultrasonographic features of synovial inflammation and vascularity during antiTNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints or TNF-driven regulation of Th17 cell production. |
| spellingShingle | Hull, D Cooksley, H Chokshi, S Williams, R Abraham, S Taylor, P Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title | Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title_full | Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title_fullStr | Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title_full_unstemmed | Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title_short | Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
| title_sort | increase in circulating th17 cells during anti tnf therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis |
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