Cameron Rankin1, Peter Grayson2, Bates Gribbons3, Kaitlin Quinn4, Christopher Redmond5 and Wanxia Tsai1, 1NIAMS/NIH, Bethesda, MD, 2National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, 3McGovern Medical School, Colleyville, TX, 4National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Washington, DC, 5National Institutes of Health, Rockville, MD
Background/Purpose: 18FDG-PET imaging can be used to directly assess vascular inflammation; however, limited access to this technology has restricted widespread adoption of this modality in clinical practice. Biomarkers of disease activity in blood to complement clinical assessment are needed in Takayasu's arteritis (TAK). This study aimed to assess biomarkers in serum of patients with TAK in relation to disease activity as defined by clinical and imaging-based assessments.
Methods: All patients in a prospective observational cohort underwent standardized clinical assessment and FDG-PET per an imaging protocol. Disease activity was defined based on clinical assessment and FDG-PET findings. Active disease was defined as clinical disease activity supported by vascular inflammation on FDG-PET. Subclinical disease was defined as active vasculitis by FDG-PET in the absence of clinical disease activity. Remission was defined as an absence of clinical disease activity with no vasculitis identified by FDG-PET. Patients who fulfilled classification criteria for TAK were purposefully selected to represent a range of disease activity states. Serum from age-matched healthy controls (HCs) were included. All clinical assessments and sample collections were performed within 24 hours of 18FDG-PET imaging. Serum chemokine/cytokine levels were evaluated through a 48-panel multiplex assay. Vascular inflammation was quantified using the PET Vascular Activity Score (PETVAS) and correlated with serum chemokine/cytokine levels using Spearman's correlation. Differences between chemokine/cytokine levels from patients with TAK and controls were assessed using Mann-Whitney test or the Kruskal-Wallis test, as appropriate. P-value < 0.05 defined statistical significance.
Results: Patients with Takayasu's arteritis (n=47) and HCs (n=12) were included. Patients had active disease (n=23), subclinical disease (n=15), or were in remission (n=9). IL-4, IL-6, IL-17, IL12p40, MIP-1a, and HGF were significantly elevated in TAK patients independent of disease status when compared to HCs. Specifically, IL-4, IL-6, and IL-12p40 were significantly elevated in active disease compared to HCs. SDF-1a was elevated in TAK patients in remission compared to active and subclinical disease (p=0.02, for each). The two markers associated best with disease activity states were IL-17 and IL-12p40, as expression was highest in active disease followed by subclinical disease then remission. No marker was positively correlated with PETVAS. IL-2, IL-8, IL-16, IL-18, IP-10, MIP-1a, and SDF-1a were significantly negatively correlated with PETVAS.
Conclusion: Serum biomarkers in patients with TAK can define disease and disease activity status. IL-17 and IL-12p40 are fundamental cytokines in TAK and track best with disease activity defined by clinical and imaging-based assessment. Cytokines involved in Th1/Th17 pathways, and surprisingly Th2 mediated responses, were identified in association with TAK. Several anti-inflammatory cytokines were identified that negatively correlate with vascular inflammation as assessed by FDG-PET, but no markers were identified in serum that were positively associated with vascular inflammation.
Disclosures: C. Rankin, None; P. Grayson, None; B. Gribbons, None; K. Quinn, None; C. Redmond, None; W. Tsai, None.
