Po-Ku Chen1,2, Joung-Liang Lan2,3,4, Ju-Pi Li2,3, Ching-Kun Chang1,2, Shih-Hsin Chang2,4, Po-Hao Huang2,4, Kai-Jieh Yeo2,4, Der-Yuan Chen5,6,7,8. 1. Translational Medicine Laboratory, Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. 2. College of Medicine, China Medical University, Taichung, Taiwan. 3. Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. 4. Rheumatology and Immunology Center, China Medical University Hospital, No. 2, Yude Road, Taichung, 40447, Taiwan. 5. Translational Medicine Laboratory, Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. dychen1957@gmail.com. 6. College of Medicine, China Medical University, Taichung, Taiwan. dychen1957@gmail.com. 7. Rheumatology and Immunology Center, China Medical University Hospital, No. 2, Yude Road, Taichung, 40447, Taiwan. dychen1957@gmail.com. 8. Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan. dychen1957@gmail.com.
Abstract
OBJECTIVES: With galectin-3 playing an important role in inflammatory responses, elevated galectin-3 levels have been shown in patients with autoimmune diseases. However, there are limited data regarding galectin-3 expression in patients with autoinflammatory diseases such as adult-onset Still's disease (AOSD). This study aimed to investigate the extracellular galectin-3 expression and examine its association with activity parameters and disease outcome in AOSD patients. METHOD: Plasma levels of galectin-3 and inflammasome downstream cytokines including interleukin (IL)-1β and IL-18 were determined by ELISA in 42 active AOSD patients and 20 healthy controls (HC). The protein levels of galectin-3 and cytokines were determined using immunoblotting. RESULTS: Plasma levels of galectin-3 and inflammasome downstream cytokines including IL-1β and IL-18 were significantly higher in AOSD patients (median 5.02 ng/ml, interquartile range [IQR] 3.12-7.88 ng/ml; 3.42 pg/ml, IQR 1.48-6.70 pg/ml; and 5758 pg/ml, IQR 859-11,895 pg/ml, respectively) compared with HC (1.86 ng/ml, IQR 1.09-2.89 ng/ml; 0.99 pg/ml, IQR 0.62-1.35 pg/ml; and 129 pg/ml, IQR 71-155 pg/ml, respectively, all p < 0.001). Plasma galectin-3 levels were positively correlated with clinical activity scores, inflammatory parameters values, and the levels of IL-1β and IL-18 in AOSD patients. AOSD patients with systemic pattern had significantly higher galectin-3 levels (median 6.08 ng/ml, IQR 4.01-9.54 ng/ml) compared with those with chronic articular pattern (3.56 ng/ml, IQR 3.04-4.98 ng/ml, p < 0.05). After 6-month therapy, galectin-3 levels significantly declined, paralleling the decreases in clinical activity scores and plasma levels of IL-1β and IL-18. CONCLUSIONS: Elevated galectin-3 levels and their positive correlation with disease activity scores, inflammatory parameter, and inflammasome downstream cytokines suggest the involvement of galectin-3 in AOSD pathogenesis.Key Points• We revealed for the first time the association of plasma galectin-3 levels with AOSD activity parameters.• We explored the link between galectin-3 levels and NLRP3-inflammasome downstream cytokines in AOSD disease.
OBJECTIVES: With galectin-3 playing an important role in inflammatory responses, elevated galectin-3 levels have been shown in patients with autoimmune diseases. However, there are limited data regarding galectin-3 expression in patients with autoinflammatory diseases such as adult-onset Still's disease (AOSD). This study aimed to investigate the extracellular galectin-3 expression and examine its association with activity parameters and disease outcome in AOSD patients. METHOD: Plasma levels of galectin-3 and inflammasome downstream cytokines including interleukin (IL)-1β and IL-18 were determined by ELISA in 42 active AOSD patients and 20 healthy controls (HC). The protein levels of galectin-3 and cytokines were determined using immunoblotting. RESULTS: Plasma levels of galectin-3 and inflammasome downstream cytokines including IL-1β and IL-18 were significantly higher in AOSD patients (median 5.02 ng/ml, interquartile range [IQR] 3.12-7.88 ng/ml; 3.42 pg/ml, IQR 1.48-6.70 pg/ml; and 5758 pg/ml, IQR 859-11,895 pg/ml, respectively) compared with HC (1.86 ng/ml, IQR 1.09-2.89 ng/ml; 0.99 pg/ml, IQR 0.62-1.35 pg/ml; and 129 pg/ml, IQR 71-155 pg/ml, respectively, all p < 0.001). Plasma galectin-3 levels were positively correlated with clinical activity scores, inflammatory parameters values, and the levels of IL-1β and IL-18 in AOSD patients. AOSD patients with systemic pattern had significantly higher galectin-3 levels (median 6.08 ng/ml, IQR 4.01-9.54 ng/ml) compared with those with chronic articular pattern (3.56 ng/ml, IQR 3.04-4.98 ng/ml, p < 0.05). After 6-month therapy, galectin-3 levels significantly declined, paralleling the decreases in clinical activity scores and plasma levels of IL-1β and IL-18. CONCLUSIONS: Elevated galectin-3 levels and their positive correlation with disease activity scores, inflammatory parameter, and inflammasome downstream cytokines suggest the involvement of galectin-3 in AOSD pathogenesis.Key Points• We revealed for the first time the association of plasma galectin-3 levels with AOSD activity parameters.• We explored the link between galectin-3 levels and NLRP3-inflammasome downstream cytokines in AOSD disease.
Authors: Jijing Tian; Guoxiang Yang; Huan-Yuan Chen; Daniel K Hsu; Alexey Tomilov; Kristin A Olson; Ali Dehnad; Sarah R Fish; Gino Cortopassi; Bin Zhao; Fu-Tong Liu; M Eric Gershwin; Natalie J Török; Joy X Jiang Journal: FASEB J Date: 2016-09-14 Impact factor: 5.191
Authors: Shiro Ohshima; Stefan Kuchen; Christian A Seemayer; Diego Kyburz; Astrid Hirt; Stephanie Klinzing; Beat A Michel; Renate E Gay; Fu-Tong Liu; Steffen Gay; Michel Neidhart Journal: Arthritis Rheum Date: 2003-10