Cysteine-Rich Angiogenic Inducer 61 Serves as a Potential Serum Biomarker for the Remission of Adult-Onset Still's Disease.

Yutong Su,Xiaobing Cheng,Zhuochao Zhou,Jialin Teng,Honglei Liu,Hui Shi,Yue Sun,Chengde Yang,Junna Ye,Qiongyi Hu,Tienan Feng,Zhihong Wang,Fan Wang,Huihui Chi

doi:10.3389/fmed.2019.00266

Yutong Su, Xiaobing Cheng + Show 12 more

Open Access

https://doi.org/10.3389/fmed.2019.00266

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Abstract

Objective: Adult-onset Still's disease (AOSD) is a rare, polygenic, systemic autoinflammatory disease. The aim of this study is to evaluate the serum levels of cysteine-rich angiogenic inducer 61 (Cyr61), a secreted, extracellular protein in AOSD patients.Methods: A total of 60 AOSD patients (39 of active phase and 21 of inactive phase), 16 rheumatoid arthritis patients as a disease control, and 34 sex- and age-matched healthy control subjects (HC) were enrolled in the study. The data of the clinical manifestations and laboratory examinations were collected. The serum levels of Cyr61, interleukin (IL)-17, and IL-37 were detected by ELISA assay, and the serum levels of IL-10, IL-1β, IL-6, IL-18, and tumor necrosis factor (TNF)-α were examined by electrochemiluminescence assay.Results: The serum levels of Cyr61 were significantly increased in inactive AOSD than those in active patients and HCs, and the levels of Cyr61 were dramatically increased after treatment. The levels of Cyr61 were inversely correlated with systemic score, the counts of leukocyte and neutrophil, and the levels of inflammatory cytokines (IL-1β, IL-6, and IL-17). Moreover, the levels of Cyr61 were higher in patients without the clinical symptoms of fever, skin rash, sore throat, arthralgia, and lymphadenopathy compared with those in patients with these symptoms.Conclusion: The serum levels of Cyr61 were inversely correlated with disease activity in AOSD patients; thus, we proposed that Cyr61 was a biomarker for the remission of AOSD.

Highlights

Adult-onset Still’s disease (AOSD) is a rare, systemic, polygenic, autoinflammatory disorder characterized by the cardinal manifestations of fever, arthralgia or arthritis, skin rash, and increased counts of leukocytes and neutrophils [1,2,3]
To examine the serum levels of Cysteine-rich angiogenic inducer 61 (Cyr61) in AOSD, a total of 60 AOSD patients including 39 active patients and 21 inactive patients, 16 rheumatoid arthritis (RA) patients, and 34 healthy control subjects (HC) were enrolled in the current study
Using the ELISA assay, we found that the serum levels of Cyr61 were not altered in total AOSD patients (171.8 ± 63.8 pg/ml, n = 60) compared to those of HC (168.2 ± 54.9 pg/ml, n = 34, p > 0.05) (Supplementary Figure 1)

Summary

Introduction

Adult-onset Still’s disease (AOSD) is a rare, systemic, polygenic, autoinflammatory disorder characterized by the cardinal manifestations of fever, arthralgia or arthritis, skin rash, and increased counts of leukocytes and neutrophils [1,2,3]. As the clinical manifestations of AOSD are consistent with several key common features of autoinflammatory diseases, it has been considered as the archetype of non-familial, polygenic, systemic autoinflammatory diseases in recent years [1] Danger signals such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) are transmitted to macrophages and neutrophils that activate specific inflammasomes, leading to the production of IL-1β and IL-18. This process leads to intense innate immune cell activation and overproduction of several proinflammatory cytokines, including IL-6, IL-8, IL-17, and tumor necrosis factor (TNF)-α. Our previous study showed that microRNAs were potential biomarkers to distinguish AOSD from sepsis [11]

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