Effector CD4+ T cell subsets in Takayasu arteritis - Differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of 6 patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (p=0.031 and p=0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (p=0.016 and p=0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho=-0.610 and rho=-0.463, respectively) and with Th17 cells (rho=-0.365 and rho=-0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

A retrospective cohort study to assess PET-CT findings and clinical outcomes in Takayasu arteritis: does 18F-fluorodeoxyglucose uptake in arteries predict relapses?

The objective of this study is to investigate the use of PET-CT scan with 18F-fluorodeoxyglucose (18F-FDG) as a method to predict outcomes in patients with Takayasu arteritis (TAK), as well as to analyze associations between 18F-FDG PET-CT findings with disease relapses, sustained remission, new angiographic lesions, ischemic events, and changes in therapy for TAK. At baseline assessment, 36 TAK patients underwent 18F-FDG PET-CT scan and maximal standardized uptake value (SUVmax) in arteries ≥ 1.3 was predictive for clinical disease activity. Thirty-two TAK patients were then followed-up for a median 83.5 months. Twenty-three (71.9%) patients developed clinical relapses and new arterial lesions were observed in 14 (43.8%) cases. Disease relapses [85.0% vs. 50.0%, p = 0.049; odds ratio (OR): 5.667; 95% confidence interval (95 CI): 1.067-30.085] and the need for changing immunosuppressive therapy (85.0% vs. 41.7%, p = 0.018; OR: 7.933; 95CI: 1.478-42.581) were more frequently found in patients with SUVmax ≥ 1.3 at baseline compared with those presenting SUVmax < 1.3. No associations were found between SUVmax ≥ or < 1.3 in large arteries at baseline and the development of ischemic events, sustained remission or new angiographic lesions. In multivariate analysis, associations between baseline SUVmax ≥ 1.3 and disease relapses were not independent (hazard ratio: 1.07; 95 CI 0.39-2.92; p = 0.892). In conclusion, arterial SUVmax is marginally associated with disease relapses and with the need to change therapy in TAK. 18F-FDG uptake in large arteries is not associated with the development of new arterial lesions in TAK.

Translation and validation of the Indian Takayasu clinical activity score (ITAS2010) for the Brazilian Portuguese language.

BACKGROUND: The Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil. METHODS: For this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement. RESULTS: The correlation coefficient for the ITAS2010 score between the two raters was high (r = 0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828-0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r = 0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292-0.790). The ITAS2010 at baseline was compared with the physician's global assessment (PGA) and with Kerr's criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0-3.0) vs. 0.0 (0.0-0.0); p = 0.0025]. Patients with active disease according to the Kerr's criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0-7.0) vs. 0.0 (0.0-0.0); p = 0.0068]. CONCLUSIONS: The Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.

Translation and validation of the Indian Takayasu clinical activity score (ITAS2010) for the Brazilian Portuguese language

Abstract Background: The Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil. Methods: For this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement. Results: The correlation coefficient for the ITAS2010 score between the two raters was high (r =0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828-0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r =0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292-0.790). The ITAS2010 at baseline was compared with the physician's global assessment (PGA) and with Kerr's criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0-3.0) vs. 0.0 (0.0-0.0); p = 0.0025]. Patients with active disease according to the Kerr's criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0-7.0) vs. 0.0 (0.0-0.0); p = 0.0068]. Conclusions: The Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.

Silent arterial inflammation during the apparent remission state of Takayasu's arteritis. What do cytokines tell us?

OBJECTIVES: To evaluate serum cytokines as biomarkers of smoldering disease activity in patients with Takayasu's arteritis (TAK) in remission. METHODS: Thirty-four TAK patients with stable disease during the last 6 months and 22 healthy controls (HC) were included in a cross-sectional study. Serum levels of pro-inflammatory, anti-inflammatory, Th1, Th2, Th9, Th17 and Th22 cytokines were measured by the multiplex technique. RESULTS: No significant differences regarding serum cytokine levels were found between TAK patients and HC. Serum TNF-α, IL-17F, IL-21 and IL-23 were higher in patients presenting angiographic type V than in those presenting other angiographic types. Serum IL-17E, IL-17F, IL-22 and IL-23 were higher in TAK patients with previous ischaemic events compared with those without previous ischaemia. No differences in serum cytokines were observed between TAK patients with and without aneurysmal disease in the aorta or among TAK patients without therapy, those under immunosuppressive agents and patients on biological therapy. Independent associations were found regarding angiographic type V and higher serum levels of IL-4, IL-6, IL17A, IL-17E, IL-17F, IL-21, IL-22 and IL-23. Previous ischaemic events were independently associated with higher serum IL-4, IL-17E, IL-22 and IL-23. Daily prednisone dose had an inverse association with lower serum IL-4, IL6, IL-17A, IL-17E, IL-22 and IL-23. The simultaneous use of immunosuppressive and biological agents led to lower serum IL-4, IL-17E and IL-23 levels. CONCLUSIONS: A smoldering inflammatory response with predominantly cytokines involved in Th17 response seems to be ongoing in TAK patients in remission with extensive disease or with previous ischaemic events.

Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?

There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.