Background/Purpose: The definition of remission in Takayasu arteritis (TA) is a challenge in clinical practice, since smoldering arterial inflammation may occur without overt signs and symptoms of disease activity in TA. There is an unmet need for biomarkers in TA to predict disease progression in patients considered in remission. Thus, this study aims to evaluate serum cytokines in TA patients and to analyze associations with disease phenotypes and therapy during the remission state.

Methods: Thirty-four consecutive TA patients with stable disease during the last 6 months were evaluated for serum levels of pro-inflammatory (TNFα, IL-1β, IL-6), anti-inflammatory (IL-2, IL-10), Th1 (IL-12, IFNγ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17A, IL-17E, IL-17F, IL-21, IL-23) and Th22 (IL-22) cytokines by the multiplex technique.

Results: Serum TNFα, IL-17F, IL-21 and IL-23 were significantly higher in patients with stable disease presenting angiographic type V compared with other angiographic types while serum IL-17E, IL-17F, IL-22 and IL-23 were higher in TA patients with previous ischemic events. Similar levels of cytokines were observed in TA patients with and without aortic aneurysmal disease, and in TA patients with and without therapy with prednisone, immunosuppressive or biological agents. However, by multivariate linear regression analysis, serum IL-4 (β = 0.064; p = 0.004), IL-6 (β = 14.12; p = 0.006), IL-17A (β = 11.09; p = 0.012), IL-17E (β = 0.064; p = 0.003), IL-17F (β = 0.028; p = 0.016), IL-21 (β = 26.16; p = 0.007), IL-22 (β = 0.062; p = 0.012) and IL-23 (β = 1.86; p = 0.002) levels were independently associated with angiographic type V. Moreover, an independent association was also found between ischemic events and serum IL-17E (β = 0.044; p = 0.005), IL-22 (β = 0.039; p = 0.029) and IL-23 (β = 1.16; p = 0.006). Daily prednisone dose was associated with lower serum IL-4 (β = -0.002; p = 0.002), IL-6 (β = -0.28; p = 0.010), IL-17A (β = -0.22; p = 0.021), IL-17E (β = -0.001; p = 0.003), IL-22 (β = -0.001; p = 0.011) and IL-23 levels (β = -0.03; p = 0.005), whereas the use of an immunosuppressive simultaneously with a biological agent led to lower serum IL-4 (β = -0.044; p = 0.024), IL-17E (β = -0.046; p = 0.017) and IL-23 (β = -0.98; p = 0.048) levels.

Conclusion: A predominant Th17 response seems to be ongoing in TA patients with extensive arterial involvement (i.e. angiographic type V) or previous ischemic events, despite the remission state. Therapy has a significant impact on serum levels of several cytokines in TA. These findings highlight the potential role of Th17 response in the pathophysiology of TA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/measurement-of-serum-cytokines-during-the-apparent-remission-state-of-takayasu-arteritis-what-do-cytokines-tell-us/