Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease

C-type lectin domain family 5-member A (CLEC5A) associates with adaptor DAP12 (DNAX activation protein 12) to form receptor complexes involved in inflammatory responses. We postulated a potential role of CLEC5A in the pathogenesis of adult-onset Still’s disease (AOSD) and aimed to investigate CLEC5A...

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Main Authors: Po-Ku Chen, Shie-Liang Hsieh, Joung-Liang Lan, Chi-Chen Lin, Shih-Hsin Chang, Der-Yuan Chen
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/9473497
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author Po-Ku Chen
Shie-Liang Hsieh
Joung-Liang Lan
Chi-Chen Lin
Shih-Hsin Chang
Der-Yuan Chen
author_facet Po-Ku Chen
Shie-Liang Hsieh
Joung-Liang Lan
Chi-Chen Lin
Shih-Hsin Chang
Der-Yuan Chen
author_sort Po-Ku Chen
collection DOAJ
description C-type lectin domain family 5-member A (CLEC5A) associates with adaptor DAP12 (DNAX activation protein 12) to form receptor complexes involved in inflammatory responses. We postulated a potential role of CLEC5A in the pathogenesis of adult-onset Still’s disease (AOSD) and aimed to investigate CLEC5A expression and its association with activity parameters and disease course. In 34 AOSD patients and 12 healthy controls (HC), circulating levels of CLEC5A-expressing monocytes or granulocytes were determined by flow cytometry analysis, the mRNA expression of CLEC5A and DAP12 on PBMCs by quantitative PCR, and plasma levels of proinflammatory cytokines by ELISA. AOSD patients had significantly higher percentages and mean fluorescence intensity (MFI) of CLEC5A-expressing monocytes (median 62.1% and 3.20, respectively) or granulocytes (72.6% and 3.22, respectively) compared with HC (in monocytes: 17.0% and 0.65, both p<0.001; in granulocytes: 67.3%, p<0.05 and 0.90, p<0.001; respectively). Patients also had significantly higher levels of CLEC5A mRNA expression on PBMCs compared with HC (median 1.77 vs. 0.68, p<0.05). The levels of CLEC5A-expressing monocytes or granulocytes were positively associated with activity scores and levels of IL-1β and IL-18 in AOSD patients. The patients with a systemic pattern had significantly higher levels of CLEC5A-expressing granulocytes and IL-18 compared to those with a chronic articular pattern of disease course. After 6 months of therapy, levels of CLEC5A-expressing monocytes and granulocytes significantly declined, paralleling the decrease of AOSD activity. Elevated CLEC5A levels and their positive association with activity parameters suggest that CLEC5A is involved in the pathogenesis and may serve as an activity indicator of AOSD.
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spelling doaj-art-bd2d19181ebb47798cf29cb8d135b5602025-08-20T03:23:19ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/94734979473497Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s DiseasePo-Ku Chen0Shie-Liang Hsieh1Joung-Liang Lan2Chi-Chen Lin3Shih-Hsin Chang4Der-Yuan Chen5Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanTranslational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanC-type lectin domain family 5-member A (CLEC5A) associates with adaptor DAP12 (DNAX activation protein 12) to form receptor complexes involved in inflammatory responses. We postulated a potential role of CLEC5A in the pathogenesis of adult-onset Still’s disease (AOSD) and aimed to investigate CLEC5A expression and its association with activity parameters and disease course. In 34 AOSD patients and 12 healthy controls (HC), circulating levels of CLEC5A-expressing monocytes or granulocytes were determined by flow cytometry analysis, the mRNA expression of CLEC5A and DAP12 on PBMCs by quantitative PCR, and plasma levels of proinflammatory cytokines by ELISA. AOSD patients had significantly higher percentages and mean fluorescence intensity (MFI) of CLEC5A-expressing monocytes (median 62.1% and 3.20, respectively) or granulocytes (72.6% and 3.22, respectively) compared with HC (in monocytes: 17.0% and 0.65, both p<0.001; in granulocytes: 67.3%, p<0.05 and 0.90, p<0.001; respectively). Patients also had significantly higher levels of CLEC5A mRNA expression on PBMCs compared with HC (median 1.77 vs. 0.68, p<0.05). The levels of CLEC5A-expressing monocytes or granulocytes were positively associated with activity scores and levels of IL-1β and IL-18 in AOSD patients. The patients with a systemic pattern had significantly higher levels of CLEC5A-expressing granulocytes and IL-18 compared to those with a chronic articular pattern of disease course. After 6 months of therapy, levels of CLEC5A-expressing monocytes and granulocytes significantly declined, paralleling the decrease of AOSD activity. Elevated CLEC5A levels and their positive association with activity parameters suggest that CLEC5A is involved in the pathogenesis and may serve as an activity indicator of AOSD.http://dx.doi.org/10.1155/2020/9473497
spellingShingle Po-Ku Chen
Shie-Liang Hsieh
Joung-Liang Lan
Chi-Chen Lin
Shih-Hsin Chang
Der-Yuan Chen
Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
Journal of Immunology Research
title Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
title_full Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
title_fullStr Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
title_full_unstemmed Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
title_short Elevated Expression of C-Type Lectin Domain Family 5-Member A (CLEC5A) and Its Relation to Inflammatory Parameters and Disease Course in Adult-Onset Still’s Disease
title_sort elevated expression of c type lectin domain family 5 member a clec5a and its relation to inflammatory parameters and disease course in adult onset still s disease
url http://dx.doi.org/10.1155/2020/9473497
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