OBJECTIVE: Takayasu arteritis (TAK) increases vascular stiffness and arterial resistance. Abnormal immune response is a crucial factor in the pathogenesis of TAK. Here, we investigated I) vascular and cardiac ultrasonography parameters as increased cardiovascular risk in TAK patients, compared to atherosclerotic patients; ii) Treg and Th17 cells frequencyin TAK-refractory patients treated with infliximab. DESIGN AND METHOD: Clinical, instrumental and biochemical data in patients with active TAK were compared in a case control study were compared to age- and sex-matched atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells percentage was measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were carried out in all patients. Histological and immunohistochemical analysis were performed to correlate vessel wall patho-morphology and clinical/laboratory results. RESULTS: TAK patients displayed increased aortic valve dysfunction and diastolic dysfunction compared to atherosclerosis. Moderate-to-severe aortic regurgitation correlates with the highest serum levels of uric acid in TAK patients. A significant increase in aortic stiffness was associated with peripheral T lymphocyte levels. Increase in CD3+CD4+ and CD8+ infiltration and High-mobility group box 1 (HMGB1) was significantly higher in TAK group. CD15+ neutrophils were significantly higher in TAK, suggesting an association with inflammation-related vascular damage. Flow cytometric Tregs percentage was significantly reduced in TAK patients. Interestingly, in patients treated with infliximab, this value significantly increased at T18 compared to T0. Concomitantly, the frequency of CD3+CD4+IL-17+ cells behaved in the opposite way: the higher number of Th17 cells observed in TAK patients at T0 compared to controls significantly decreased at T18 compared to T0.Supporting the specific pathogenetic mechanisms of vessel damage in TAK, we found an increased risk of cardiovascular disease that correlates directly with the degree of inflammatory cell infiltration in the vessel wall. CONCLUSIONS: These observations strengthen the clinical efficacy of infliximab in TAK patients, supporting the idea that biologic therapy may achieve a better control of TAK progression and help to stabilize the Treg/Th17 score toward values similar to those found in atherosclerotic patients. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved

CORRELATION BETWEEN VASCULAR INFLAMMATION MARKERS, DIASTOLIC DYSFUNCTION AND CARDIOVASCULAR RISK IN PATIENTS WITH TAKAYASU ARTERITIS

Cicco S.;Desantis V.;Vacca A.;Cazzato G.;Solimando A. G.;Susca C.;Lamanuzzi A.;Saltarella I.;Ingravallo G.;Resta L.;Ranieri G.;Montagnani M.;Ria R.
2022

Abstract

OBJECTIVE: Takayasu arteritis (TAK) increases vascular stiffness and arterial resistance. Abnormal immune response is a crucial factor in the pathogenesis of TAK. Here, we investigated I) vascular and cardiac ultrasonography parameters as increased cardiovascular risk in TAK patients, compared to atherosclerotic patients; ii) Treg and Th17 cells frequencyin TAK-refractory patients treated with infliximab. DESIGN AND METHOD: Clinical, instrumental and biochemical data in patients with active TAK were compared in a case control study were compared to age- and sex-matched atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells percentage was measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were carried out in all patients. Histological and immunohistochemical analysis were performed to correlate vessel wall patho-morphology and clinical/laboratory results. RESULTS: TAK patients displayed increased aortic valve dysfunction and diastolic dysfunction compared to atherosclerosis. Moderate-to-severe aortic regurgitation correlates with the highest serum levels of uric acid in TAK patients. A significant increase in aortic stiffness was associated with peripheral T lymphocyte levels. Increase in CD3+CD4+ and CD8+ infiltration and High-mobility group box 1 (HMGB1) was significantly higher in TAK group. CD15+ neutrophils were significantly higher in TAK, suggesting an association with inflammation-related vascular damage. Flow cytometric Tregs percentage was significantly reduced in TAK patients. Interestingly, in patients treated with infliximab, this value significantly increased at T18 compared to T0. Concomitantly, the frequency of CD3+CD4+IL-17+ cells behaved in the opposite way: the higher number of Th17 cells observed in TAK patients at T0 compared to controls significantly decreased at T18 compared to T0.Supporting the specific pathogenetic mechanisms of vessel damage in TAK, we found an increased risk of cardiovascular disease that correlates directly with the degree of inflammatory cell infiltration in the vessel wall. CONCLUSIONS: These observations strengthen the clinical efficacy of infliximab in TAK patients, supporting the idea that biologic therapy may achieve a better control of TAK progression and help to stabilize the Treg/Th17 score toward values similar to those found in atherosclerotic patients. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/408759
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