Skip to main content
Erschienen in: Clinical Rheumatology 11/2020

09.05.2020 | Original Article

The value of interleukin-6 in predicting disease relapse for Takayasu arteritis during 2-year follow-up

verfasst von: Ying Sun, Xiufang Kong, Xiaomeng Cui, Xiaomin Dai, Lili Ma, Huiyong Chen, Rongyi Chen, Peng Lv, Jiang Lin, Qingrong Huang, Xuejuan Jin, Lindi Jiang

Erschienen in: Clinical Rheumatology | Ausgabe 11/2020

Einloggen, um Zugang zu erhalten

Abstract

Objective

To evaluate the value of interleukin-6 (IL-6) in predicting long-term disease prognosis for Takayasu arteritis (TA).

Methods

Sixty-seven TA patients, who had IL-6 levels detected at the first visit and had a regular follow-up of at least 2 years, were enrolled. Data recorded up to March 31, 2019, including clinical presentations, laboratory indices, treatments, and radiological images were collected and used for analysis. The value of IL-6 in predicting disease relapse and imaging progression was analyzed.

Results

IL-6 levels were positively related with disease activity index, including Kerr scores, C-reactive protein (CRP) levels. Patients were divided into three groups according to baseline serum IL-6 levels: low group (< 5.4 pg/mL, n = 29), medium group (5.4–11.5 pg/mL, n = 20), and high group (> 11.5 ng/mL, n = 18). Patients in the medium and high group had higher disease activity than those in the low group (p < 0.01). Baseline IL-6 levels were correlated with luminal stenosis (p < 0.05), although no significant correlations with long-term imaging progression were observed. Patients with more than 2 episodes of disease relapses were most commonly seen in the medium group (p < 0.05). Multivariate Cox proportional hazard regression analysis indicated that medium and high IL-6 levels were positive predictors for disease relapse (HR 4.3, 95%CI 1.3–18.7 p = 0.07 for medium group; HR 2.1, 95% CI 0.7–48.9, p = 0.19 for high group) with disease status and treatment adjusted.

Conclusions

IL-6 may be a valuable predictor of TA disease relapse during long-term follow-up. Treatments targeted at IL-6 pathways might reduce disease relapse and have better prognostic effects for TA.
Key Points
• Positive relationships between IL-6 levels and disease activity index, including Kerr scores, C-reactive protein (CRP) levels, etc. were indicated.
• Medium and high baseline IL-6 levels were valuable for predicting disease relapse during the 2-year follow-up.
• Baseline IL-6 levels were positively correlated with luminal stenosis on imaging.
Literatur
1.
Zurück zum Zitat Yang L, Zhang H, Jiang X, Zou Y, Qin F, Song L, Guan T, Wu H, Xu L, Liu Y, Zhou X, Bian J, Hui R, Zheng D (2014) Clinical manifestations and long-term outcome for patients with Takayasu arteritis in China. J Rheumatol 41:2439–2446CrossRef Yang L, Zhang H, Jiang X, Zou Y, Qin F, Song L, Guan T, Wu H, Xu L, Liu Y, Zhou X, Bian J, Hui R, Zheng D (2014) Clinical manifestations and long-term outcome for patients with Takayasu arteritis in China. J Rheumatol 41:2439–2446CrossRef
2.
Zurück zum Zitat Yilmaz N, Can M, Oner FA, Kalfa M, Emmungil H, Karadag O, Yildiz F, Kimyon G, Yilmazer B, Gerdan V, Bilge SY, Ilhan B, Cobankara V, Kasifoglu T, Cefle A, Kisacik B, Onat AM, Akar S, Onen F, Erken E, Kiraz S, Aksu K, Keser G, Mumcu G, Direskeneli H (2013) Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatology (Oxford) 52:1898–1904CrossRef Yilmaz N, Can M, Oner FA, Kalfa M, Emmungil H, Karadag O, Yildiz F, Kimyon G, Yilmazer B, Gerdan V, Bilge SY, Ilhan B, Cobankara V, Kasifoglu T, Cefle A, Kisacik B, Onat AM, Akar S, Onen F, Erken E, Kiraz S, Aksu K, Keser G, Mumcu G, Direskeneli H (2013) Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatology (Oxford) 52:1898–1904CrossRef
3.
Zurück zum Zitat Watanabe Y, Miyata T, Tanemoto K (2015) Current clinical features of new patients with Takayasu arteritis observed from a cross-country research in Japan: age and sex specificity. Circulation 132:1701–1709CrossRef Watanabe Y, Miyata T, Tanemoto K (2015) Current clinical features of new patients with Takayasu arteritis observed from a cross-country research in Japan: age and sex specificity. Circulation 132:1701–1709CrossRef
4.
Zurück zum Zitat Kerr FS, Hallahan CW, Gordano J et al (1994) Takayasu arteritis. Ann Intern Med 120:919–929CrossRef Kerr FS, Hallahan CW, Gordano J et al (1994) Takayasu arteritis. Ann Intern Med 120:919–929CrossRef
5.
Zurück zum Zitat Misra R, Danda D, Rajappa SM, Ghosh A, Gupta R, Mahendranath KM, Jeyaseelan L, Lawrence A, Bacon PA, Indian Rheumatology Vasculitis (IRAVAS) group (2013) Development and initial validation of the Indian Takayasu clinical activity score (ITAS2010). Rheumatology (Oxford) 52:1795–1801CrossRef Misra R, Danda D, Rajappa SM, Ghosh A, Gupta R, Mahendranath KM, Jeyaseelan L, Lawrence A, Bacon PA, Indian Rheumatology Vasculitis (IRAVAS) group (2013) Development and initial validation of the Indian Takayasu clinical activity score (ITAS2010). Rheumatology (Oxford) 52:1795–1801CrossRef
6.
Zurück zum Zitat Alibaz-Oner F, Aydin SZ, Akar S, Aksu K, Kamali S, Yucel E, Karadag O, Ozer H, Kiraz S, Onen F, Inanc M, Keser G, Akkoc N, Direskeneli H (2015) Assessment of patients with Takayasu arteritis in routine practice with Indian Takayasu clinical activity score. J Rheumatol 42:1443–1447CrossRef Alibaz-Oner F, Aydin SZ, Akar S, Aksu K, Kamali S, Yucel E, Karadag O, Ozer H, Kiraz S, Onen F, Inanc M, Keser G, Akkoc N, Direskeneli H (2015) Assessment of patients with Takayasu arteritis in routine practice with Indian Takayasu clinical activity score. J Rheumatol 42:1443–1447CrossRef
7.
Zurück zum Zitat Ma LY, Li CL, Ma LL et al (2019) Value of contrast-enhanced ultrasonography of the carotid artery for evaluating disease activity in Takayasu arteritis. Arthritis Res Ther 21:24CrossRef Ma LY, Li CL, Ma LL et al (2019) Value of contrast-enhanced ultrasonography of the carotid artery for evaluating disease activity in Takayasu arteritis. Arthritis Res Ther 21:24CrossRef
8.
Zurück zum Zitat Chung JW, Kim HC, Choi YH, Kim SJ, Lee W, Park JH (2007) Patterns of aortic involvement in Takayasu arteritis and its clinical implications: evaluation with spiral computed tomography angiography. J Vasc Surg 45:906–914CrossRef Chung JW, Kim HC, Choi YH, Kim SJ, Lee W, Park JH (2007) Patterns of aortic involvement in Takayasu arteritis and its clinical implications: evaluation with spiral computed tomography angiography. J Vasc Surg 45:906–914CrossRef
9.
Zurück zum Zitat Jiang L, Li D, Yan F, Dai X, Li Y, Ma L (2012) Evaluation of Takayasu arteritis activity by delayed contrast-enhanced magnetic resonance imaging. Int J Cardiol 155:262–267CrossRef Jiang L, Li D, Yan F, Dai X, Li Y, Ma L (2012) Evaluation of Takayasu arteritis activity by delayed contrast-enhanced magnetic resonance imaging. Int J Cardiol 155:262–267CrossRef
10.
Zurück zum Zitat Germano G, Monti S, Ponte C et al (2017) The role of ultrasound in the diagnosis and follow-up of large-vessel vasculitis: an update. Clin Exp Rheumatol 35(Suppl):194–198PubMed Germano G, Monti S, Ponte C et al (2017) The role of ultrasound in the diagnosis and follow-up of large-vessel vasculitis: an update. Clin Exp Rheumatol 35(Suppl):194–198PubMed
11.
Zurück zum Zitat Zhang X, Zhou J, Sun Y, Shi H, Ji Z, Jiang L (2018) 18F-FDG-PET/CT: an accurate method to assess the activity of Takayasu’s arteritis. Clin Rheumatol 37:1927–1935CrossRef Zhang X, Zhou J, Sun Y, Shi H, Ji Z, Jiang L (2018) 18F-FDG-PET/CT: an accurate method to assess the activity of Takayasu’s arteritis. Clin Rheumatol 37:1927–1935CrossRef
12.
Zurück zum Zitat Tamura N, Maejima Y, Tezuka D, Takamura C, Yoshikawa S, Ashikaga T, Hirao K, Isobe M (2017) Profiles of serum cytokine levels in Takayasu arteritis patients: potential utility as biomarkers for monitoring disease activity. J Cardiol 70:278–285CrossRef Tamura N, Maejima Y, Tezuka D, Takamura C, Yoshikawa S, Ashikaga T, Hirao K, Isobe M (2017) Profiles of serum cytokine levels in Takayasu arteritis patients: potential utility as biomarkers for monitoring disease activity. J Cardiol 70:278–285CrossRef
13.
Zurück zum Zitat Sun Y, Ma L, Yan F, Liu H, Ding Y, Hou J, Jiang L (2012) MMP-9 and IL-6 are potential biomarkers for disease activity in Takayasu’s arteritis. Int J Cardiol 156:236–238CrossRef Sun Y, Ma L, Yan F, Liu H, Ding Y, Hou J, Jiang L (2012) MMP-9 and IL-6 are potential biomarkers for disease activity in Takayasu’s arteritis. Int J Cardiol 156:236–238CrossRef
14.
Zurück zum Zitat Matsuyama A, Sakai N, Ishigami M, Hiraoka H, Kashine S, Hirata A, Nakamura T, Yamashita S, Matsuzawa Y (2003) Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation 108:1469–1473CrossRef Matsuyama A, Sakai N, Ishigami M, Hiraoka H, Kashine S, Hirata A, Nakamura T, Yamashita S, Matsuzawa Y (2003) Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation 108:1469–1473CrossRef
15.
Zurück zum Zitat Ishihara T, Haraguchi G, Kamiishi T, Tezuka D, Inagaki H, Isobe M (2011) Sensitive assessment of activity of Takayasu's arteritis by pentraxin3, a new biomarker. J Am Coll Cardiol 57:1712–1713CrossRef Ishihara T, Haraguchi G, Kamiishi T, Tezuka D, Inagaki H, Isobe M (2011) Sensitive assessment of activity of Takayasu's arteritis by pentraxin3, a new biomarker. J Am Coll Cardiol 57:1712–1713CrossRef
16.
Zurück zum Zitat Alibaz-Oner F, Aksu K, Yentur SP, Keser G, Saruhan-Direskeneli G, Direskeneli H (2016) Plasma pentraxin-3 levels in patients with Takayasu’s arteritis during routine follow-up. Clin Exp Rheumatol 34:s73–s76PubMed Alibaz-Oner F, Aksu K, Yentur SP, Keser G, Saruhan-Direskeneli G, Direskeneli H (2016) Plasma pentraxin-3 levels in patients with Takayasu’s arteritis during routine follow-up. Clin Exp Rheumatol 34:s73–s76PubMed
17.
Zurück zum Zitat Kong X, Sun Y, Ma L, Chen H, Wei L, Wu W, Ji Z, Ma L, Zhang Z, Zhang Z, Zhao Z, Hou J, Dai S, Yang C, Jiang L (2016) The critical role of IL-6 in the pathogenesis of Takayasu arteritis. Clin Exp Rheumatol 34:S21–S27PubMed Kong X, Sun Y, Ma L, Chen H, Wei L, Wu W, Ji Z, Ma L, Zhang Z, Zhang Z, Zhao Z, Hou J, Dai S, Yang C, Jiang L (2016) The critical role of IL-6 in the pathogenesis of Takayasu arteritis. Clin Exp Rheumatol 34:S21–S27PubMed
18.
Zurück zum Zitat Gao Q, Lv N, Dang A et al (2019) Association of interleukin-6 and interleukin-10 expression, gene polymorphisms, and Takayasu arteritis in a Chinese Han population. Clin Rheumatol 38:143–148CrossRef Gao Q, Lv N, Dang A et al (2019) Association of interleukin-6 and interleukin-10 expression, gene polymorphisms, and Takayasu arteritis in a Chinese Han population. Clin Rheumatol 38:143–148CrossRef
19.
Zurück zum Zitat Alibaz-Oner F, Yentur SP, Saruhan-Direskeneli G et al (2015) Serum cytokine profiles in Takayasu’s arteritis: search for biomarkers. Clin Exp Rheumatol 33:S 32–S 35 Alibaz-Oner F, Yentur SP, Saruhan-Direskeneli G et al (2015) Serum cytokine profiles in Takayasu’s arteritis: search for biomarkers. Clin Exp Rheumatol 33:S 32–S 35
20.
Zurück zum Zitat Pulsatelli L, Boiardi L, Assirelli E et al (2017) Interleukin-6 and soluble interleukin-6 receptor are elevated in larger-vessel vasculitis: a cross-sectional and longitudinal study. Clin Exp Rheumatol 103:102–110 Pulsatelli L, Boiardi L, Assirelli E et al (2017) Interleukin-6 and soluble interleukin-6 receptor are elevated in larger-vessel vasculitis: a cross-sectional and longitudinal study. Clin Exp Rheumatol 103:102–110
21.
Zurück zum Zitat Kong X, Ma L, Ji Z, Dong Z, Zhang Z, Hou J, Zhang S, Ma L, Jiang L (2018) Pro-fibrotic effect of IL-6 via aortic adventitial fibroblasts indicates IL-6 as a treatment target in Takayasu arteritis. Clin Exp Rheumatol 36:62–72PubMed Kong X, Ma L, Ji Z, Dong Z, Zhang Z, Hou J, Zhang S, Ma L, Jiang L (2018) Pro-fibrotic effect of IL-6 via aortic adventitial fibroblasts indicates IL-6 as a treatment target in Takayasu arteritis. Clin Exp Rheumatol 36:62–72PubMed
22.
Zurück zum Zitat Chen R, Sun Y, Cui X, Ji Z, Kong X, Wu S, Huang Q, Dai X, Zhang S, Ma L, Jiang L (2019) Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu’s arteritis. J Autoimmun 99:39–47CrossRef Chen R, Sun Y, Cui X, Ji Z, Kong X, Wu S, Huang Q, Dai X, Zhang S, Ma L, Jiang L (2019) Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu’s arteritis. J Autoimmun 99:39–47CrossRef
23.
Zurück zum Zitat Arend WP, Michel BA, Bloch DA et al (1990) The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 33:1129–1134CrossRef Arend WP, Michel BA, Bloch DA et al (1990) The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 33:1129–1134CrossRef
24.
Zurück zum Zitat Hata A, Noda M, Moriwaki R et al (1996) Angiographic findings of Takayasu arteritis: new classification. Int J Cardiol 54:155–163CrossRef Hata A, Noda M, Moriwaki R et al (1996) Angiographic findings of Takayasu arteritis: new classification. Int J Cardiol 54:155–163CrossRef
25.
Zurück zum Zitat Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y (2014) Targeting interleukin-6 in inflammatory autoimmune disease and cancers. Pharmacol Ther 141:125–139CrossRef Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y (2014) Targeting interleukin-6 in inflammatory autoimmune disease and cancers. Pharmacol Ther 141:125–139CrossRef
26.
Zurück zum Zitat Manku S, Wong W, Luo Z, Seidman MA, Alabdurubalnabi Z, Rey K, Enns W, Avina-Zubieta JA, Shojania K, Choy JC (2018) IL-6 expression is correlated with increased T-cell proliferation and survival in the arterial wall in giant cell arteritis. Cardiovasc Pathol 33:55–61CrossRef Manku S, Wong W, Luo Z, Seidman MA, Alabdurubalnabi Z, Rey K, Enns W, Avina-Zubieta JA, Shojania K, Choy JC (2018) IL-6 expression is correlated with increased T-cell proliferation and survival in the arterial wall in giant cell arteritis. Cardiovasc Pathol 33:55–61CrossRef
27.
Zurück zum Zitat Burja B, Feichtinger J, Lakota K, Thallinger GG, Sodin-Semrl S, Kuret T, Rotar Ž, Ješe R, Žigon P, Čučnik S, Mali P, Praprotnik S, Tomšič M, Hočevar A (2019) Utility of serological biomarkers for giant cell arteritis in a large cohort treatment-naïve patients. Clin Rheumatol 38:317–329CrossRef Burja B, Feichtinger J, Lakota K, Thallinger GG, Sodin-Semrl S, Kuret T, Rotar Ž, Ješe R, Žigon P, Čučnik S, Mali P, Praprotnik S, Tomšič M, Hočevar A (2019) Utility of serological biomarkers for giant cell arteritis in a large cohort treatment-naïve patients. Clin Rheumatol 38:317–329CrossRef
28.
Zurück zum Zitat Kong X, Zhang X, Lv P et al (2018) Treatment of Takayasu arteritis with the IL-6R antibody tocilizumab vs. cyclophosphamide. Int J Cardiol 266:222–228CrossRef Kong X, Zhang X, Lv P et al (2018) Treatment of Takayasu arteritis with the IL-6R antibody tocilizumab vs. cyclophosphamide. Int J Cardiol 266:222–228CrossRef
29.
Zurück zum Zitat Sun Y, Ma L, Kong X et al (2017) Cyclophosphamide could be a better choice than methotrexate as induction treatment for patients with more severe Takayasu’s arteritis. Rheumatol Int 37:2019–2026CrossRef Sun Y, Ma L, Kong X et al (2017) Cyclophosphamide could be a better choice than methotrexate as induction treatment for patients with more severe Takayasu’s arteritis. Rheumatol Int 37:2019–2026CrossRef
31.
Zurück zum Zitat Yoshifuji H (2019) Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy. Mod Rheumatol 29:287–293CrossRef Yoshifuji H (2019) Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy. Mod Rheumatol 29:287–293CrossRef
32.
Zurück zum Zitat Koster MJ, Warrington KJ (2017) Giant cell arteritis: pathogenic mechanisms and new potential therapeutic targets. BMC Rheumatol 1:2CrossRef Koster MJ, Warrington KJ (2017) Giant cell arteritis: pathogenic mechanisms and new potential therapeutic targets. BMC Rheumatol 1:2CrossRef
34.
Zurück zum Zitat Adler S, Reichenbach S, Gloor A et al (2019) Risk of relapse after discontinuation of tocilizumab therapy in giant cell arteritis. Rheumatology (Oxford) 58:1939–1643CrossRef Adler S, Reichenbach S, Gloor A et al (2019) Risk of relapse after discontinuation of tocilizumab therapy in giant cell arteritis. Rheumatology (Oxford) 58:1939–1643CrossRef
35.
Zurück zum Zitat Sun Y, Kong X, Wu S, Ma L, Yan Y, Lv P, Jiang L (2019) YKL-40 as a new biomarker of disease activity in Takayasu arteritis. Int J Cardiol 293:231–237CrossRef Sun Y, Kong X, Wu S, Ma L, Yan Y, Lv P, Jiang L (2019) YKL-40 as a new biomarker of disease activity in Takayasu arteritis. Int J Cardiol 293:231–237CrossRef
36.
Zurück zum Zitat Loricera J, Bianco R, Hernandez JL et al (2016) Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review. Clin Exp Rheumatol 34:S44–S53PubMed Loricera J, Bianco R, Hernandez JL et al (2016) Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review. Clin Exp Rheumatol 34:S44–S53PubMed
37.
Zurück zum Zitat Mekinian A, Resche-Rigon M, Comarmond C, Soriano A, Constans J, Alric L, Jego P, Busato F, Cabon M, Dhote R, Estibaliz L, Koné-Paut I, Landron C, Lavigne C, Lioger B, Michaud M, Ruivard M, Sacre K, Gottenberg JE, Gaches F, Goulenok T, Salvarani C, Cacoub P, Fain O, Saadoun D, French Takayasu network (2018) Efficacy of tocilizumab in Takayasu arteritis: multicenter retrospective study of 46 patients. J Autoimmun 91:55–60CrossRef Mekinian A, Resche-Rigon M, Comarmond C, Soriano A, Constans J, Alric L, Jego P, Busato F, Cabon M, Dhote R, Estibaliz L, Koné-Paut I, Landron C, Lavigne C, Lioger B, Michaud M, Ruivard M, Sacre K, Gottenberg JE, Gaches F, Goulenok T, Salvarani C, Cacoub P, Fain O, Saadoun D, French Takayasu network (2018) Efficacy of tocilizumab in Takayasu arteritis: multicenter retrospective study of 46 patients. J Autoimmun 91:55–60CrossRef
Metadaten
Titel
The value of interleukin-6 in predicting disease relapse for Takayasu arteritis during 2-year follow-up
verfasst von
Ying Sun
Xiufang Kong
Xiaomeng Cui
Xiaomin Dai
Lili Ma
Huiyong Chen
Rongyi Chen
Peng Lv
Jiang Lin
Qingrong Huang
Xuejuan Jin
Lindi Jiang
Publikationsdatum
09.05.2020
Verlag
Springer International Publishing
Erschienen in
Clinical Rheumatology / Ausgabe 11/2020
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-020-05066-8

Weitere Artikel der Ausgabe 11/2020

Clinical Rheumatology 11/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.