Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti−TNF-α Therapy

Li, Xueyi; Chen, Lina; Wu, Zhenbiao; Han, Qin; Li, Qiang; Zhu, Ping

doi:10.1007/s10875-012-9774-0

Cited by 114 publications

(110 citation statements)

References 53 publications

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“…We have revealed that low CD4CD69 cell frequency at the initiation of anti-TNF therapy was a good predictor of treatment response to anti-TNF treatment in RA [16]. However, data are much scarcer in relation to AS, in which an increase in Th17 cell frequencies has also been revealed during anti-TNF treatment [12], but opposing results have also been obtained by others [11]. Prospective examination of T-cell subset distribution in a larger number of AS patients could help answer the question of whether these proinflammatory T-cell subsets or other T-cell subtypes may be associated with therapy resistance or may contribute to disease relapse after the withdrawal of anti-TNF treatment.…”

Section: Discussionmentioning

confidence: 99%

“…There are only few studies addressing the question of how TNF inhibitors influence the T-cell repertoire in AS [10-14]. Most of the existing examinations, however, have operated with only few T-cell subsets [10], and some of them examined only the role of T reg and/or Th17 cells [11, 12, 15]. The available articles do not make a distinction between peripheral and/or axial AS, and they use non-radiographic spondyloarthritis as an early stage of AS [10, 13] rather than as an individually existing entity.…”

Section: Introductionmentioning

confidence: 99%

“…The applied medication is often missing from the cohort descriptions. Importantly, only 1 study analyzed patients with relatively long-standing anti-TNF treatment (6 months) [11], whereas 2 further investigations, including our previous work, followed the T-cell repertoire only for a short time (6 weeks) [12, 14], although we have recently demonstrated in our study of rheumatoid arthritis (RA) patients that there are profound differences in the T-cell subset distribution after short-term or long-term follow-up [16]. …”

Section: Introductionmentioning

confidence: 99%

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The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

et al. 2017

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Objectives: Ankylosing spondylitis (AS) is a chronic, progressive immune-mediated inflammatory disease, driven primarily by Th1 and Th17 cells. Anti-TNF therapies are successfully used in AS to achieve and maintain remission. However, their influence on the composition of T-cell subsets is not clear. We aimed to characterize the changes in the T-cell repertoire after a long-term anti-TNF treatment in AS patients. Methods: Twenty-two AS patients under long-term anti-TNF therapy were evaluated (15 anti-TNF responders and 7 nonresponders). A wide range of cell subtypes was analyzed with flow cytometry and compared with therapy-naïve and short-term data too. Results: Key findings include decreased proportions of naïve CD4 and CD8 cells, increased frequencies of Th1 and Th17 cells and higher Th1/Th2 ratios in the long-term anti-TNF-treated patients (responders, nonresponders and total), which was found to be significant not only when compared with healthy controls, but also with therapy-naïve and short-term anti-TNF-treated AS patients. We noted several alterations within the various activated T-cell subsets – increase in CD4HLADR cells in responders, in CD8HLADR cells in the whole AS group and in responders, and in CD4CD25 cells in responders, and decrease in CD4CD69 cell percentages in long-term treated patients – becoming evident only after long-term anti-TNF therapy. Conclusions: This study provides a comprehensive assessment of the impact of anti-TNF therapy on the T-cell repertoire in AS. Changes in T-cell phenotype seem to develop progressively during therapy, even in inactive disease, and reflect an ongoing effector T-cell differentiation and activation, along with the parallel compensatory increase in regulatory T cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

et al. 2017

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“…В сы-воротке и плазме больных АС отмечено достоверное повы-шение концентрации ФНОα, ИЛ17, ИЛ23, ИЛ21, ИЛ6 и ИЛ8 [4,5]. На фоне лечения иФНОα при АС наблюдает-ся снижение уровней ИЛ17, Th17-клеток, ИЛ23 и ИЛ6 в крови у ответивших на терапию [46]. Концентрация ИЛ6 в крови коррелирует с индексами BASDAI и ASDAS, уров-нем СРБ и МРТ-признаками воспалительной активности заболевания [15,29,47].…”

Section: цитокины хемокины факторы ростаunclassified

Laboratory Biomarkers for Ankylosing Spondylitis

Александрова¹,

Новиков²

2017

rsp

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“…Human studies show elevated serum and synovial fluid IL-17 and also IL-23 levels in patients with AS and PsA, but their association with disease activity and response to TNFi has been inconsistent [39][40][41][42].…”

Section: Human Studiesmentioning

confidence: 99%

IL-17 Inhibition in Axial Spondyloarthritis

Danve

Deodhar

2015

Curr Treat Options in Rheum

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Opinion statementAxial spondyloarthritis (axSpA) affects 0.5-1.5 % of western population. Although TNF inhibitor (TNFi) medications have dramatically improved the treatment of this disabling disease, there are almost 40 % of patients who do not respond or have intolerance to TNFi. Several genetic, animal model, translational, and clinical studies have confirmed the role of IL-23/IL-17 pathway in the pathogenesis of the axSpA. This axis could be targeted upstream by inhibiting either IL-23 or IL-23 receptor (IL-23R) or downstream by blocking IL-17 or IL-1RA receptor. Ustekinumab, a monoclonal antibody against p40 subunit of IL-12 and IL-23, and secukinumab, a monoclonal antibody against IL-17, have both demonstrated significant beneficial effect in controlling the disease activity, quality of life, and physical function as well as MRI scores in axSpA. Combined IL-17 and TNF-α blockade is a novel option for the patients with axSpA, which needs to be investigated further. We need prospective trials to evaluate the effect of IL-23/IL-17 axis manipulation on the radiographic progression and also on the extra-articular manifestations of axSpA.

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Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti−TNF-α Therapy

Abstract: The beneficial effect of anti-TNF-α therapy in AS might not only neutralize the effects of TNF-α but also down-regulate Th17 and Th17-related cytokines accompanied by up-regulating the Treg/TGF-β axis in responders.

Cited by 114 publications

References 53 publications

The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

Laboratory Biomarkers for Ankylosing Spondylitis

IL-17 Inhibition in Axial Spondyloarthritis

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