Effect of biologics in the level of cytokines in the synovial fluid of patients with ankylosing spondylitis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions: Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.
Abstract
Background/Aims: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions: Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.
참고문헌 (27)
- McInnes IB, "Cytokines in the pathogenesis of rheumatoid arthritis", Nat Rev Immunol, 7, pp.429~442 (2007)
- Appel H, "Rheumatoid arthritis and ankylosing spondylitis : pathology of acute inflammation", Clin Exp Rheumatol, 27, pp.S15~S19 (2009)
- Smolen JS, "EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs : 2016 update", Ann Rheum Dis, 76, pp.960~977 (2017)
- van der Heijde D, "2016 Update of the ASAS-EULAR management recommendations for axial spondyloarthritis", Ann Rheum Dis, 76, pp.978~991 (2017)
- Baeten D, "Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy: histologic findings in eight patients from an open-label pilot study", Arthritis Rheum, 44, pp.186~195 (2001)
- Feldmann M, "Development of anti-TNF therapy for rheumatoid arthritis", Nat Rev Immunol, 2, pp.364~371 (2002)
- Raza K, "Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin", Arthritis Res Ther, 7, pp.R784~R795 (2005)
- Braun J, "Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study", Ann Rheum Dis, 76, pp.1070~1077 (2017)
- Coates LC, "Real life experience confirms sustained response to long-term biologics and switching in ankylosing spondylitis", Rheumatology, 47, pp.897~900 (2008)
- Deodhar A, "Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis", Semin Arthritis Rheum, 47, pp.343~350 (2017)
- Kiltz U, "Treatment of ankylosing spondylitis in patients refractory to TNF-inhibition : are there alternatives", Curr Opin Rheumatol, 24, pp.252~260 (2012)
- Aletaha D, "2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology", European League Against Rheumatism collaborative initiative, 2010, pp.69, 1580~1588
- van der Linden S, "Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria", Arthritis Rheum, 27, pp.361~368 (1984)
- Calin A, "A new approach to defining functional ability in ankylosing spondylitis : the development of the Bath Ankylosing Spondylitis Functional Index", J Rheumatol, 21, pp.2281~2285 (1994)
- Wright HL, "Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy", Rheumatology, 51, pp.451~459 (2012)
- Australo-Anglo-American Spondyloarthritis Consortium, "Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci", Nat Genet, 42, pp.123~127 (2010)
- Harrington LE, "Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages", Nat Immunol, 6, pp.1123~1132 (2005)
- Lories RJ, "Primed for inflammation : enthesis-resident T cells", Nat Med, 18, pp.1018~1019 (2012)
- Lubberts E, "The IL-23-IL-17 axis in inflammatory arthritis", Nat Rev Rheumatol, 11, pp.562~ (2015)
- Wendling D, "Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis", Joint Bone Spine, 74, pp.304~305 (2007)
- Wang X, "Expression of IL-23and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis", Rheumatol Int, 29, pp.1343~1347 (2009)
- Mei Y, "Increased serum IL-17 and IL-23in the patient with ankylosing spondylitis", Clin Rheumatol, 30, pp.269~273 (2011)
- Ziolkowska M, "High levels of IL-17 in rheumatoid arthritis patients : IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism", J Immunol, 164, pp.2832~2838 (2000)
- Singh AK, "Th-17 associated cytokines in patients with reactive arthritis", undifferentiated spondyloarthropathy, 2011, pp.30, 771~776
- Singh R, "Th1", Th17 cytokine profiles in patients with reactive arthritis, J Rheumatol, pp.2007, 34[DOI]
- Noordenbos T, "Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis", Arthritis Rheum, 64, pp.99~109 (2012)
- Singh JA, "2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis", Arthritis Rheumatol, 68, pp.1~26 (2016)
