Fibrinogen-Like Protein 1 Is a Novel Biomarker for Predicting Disease Activity and Prognosis of Rheumatoid Arthritis.

Shijia Liu,Wei Zhou,Wei Ji,Deshun Kong,Jiawei Lu,Wenfeng Tan,Lu Lu,Jue Wang,Youjuan Zhu,Tingting Xu,Yan Lu,Yunke Guo,Mengying Ke,Qiuxiang Shen,Wenjun Chen

doi:10.3389/fimmu.2020.579228

Abstract

Rheumatoid arthritis (RA), afflicting over 1% of the population, is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. Disease-modifying anti-rheumatic drugs are considered as the first-line treatment to inhibit the progression of RA, and the treatment depends on the disease status assessment. The disease activity score 28 as clinical gold standard is extensively used for RA assessment, but it has the limitations of delayed assessment and the need for specialized expertise. It is necessary to discover biomarkers that can precisely monitor disease activity, and provide optimized treatment for RA patients. A total of 1,244 participants from two independent centers were divided into five cohorts. Cohorts 1–4 constituted sera samples of moderate to high active RA, low active RA, RA in remission and healthy subjects. Cohort 5 consisted of sera of RA, osteoarthritis (OA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS) and healthy subjects. Biomarkers were found from cohorts 1–2 (screening sets), cohort 3 (discovery and external validation sets), cohort 4 (drug intervention set) and cohort 5 (biomarker-specific evaluation set). We found 68 upregulated and 74 downregulated proteins by TMT-labeled proteomics in cohort 1, and fibrinogen-like protein 1 (FGL1) had the highest area under the receiver operating characteristic curve (AUC) values in cohort 2. In cohort 3, in cross-comparison among moderate/high active RA, low active RA, RA in remission and healthy subjects, FGL1 had AUC values of approximately 0.9000 and predictive values of 90%. Additionally, FGL1 had a predictive value of 91.46% for moderate/high active RA vs. remission/low active RA and 80.77% for RA in remission vs. low active RA in cohort 4. Importantly, FGL1 levels had no significant difference in OA and AS compared with healthy persons. The concentrations in SLE and pSS were improved, but approximately 3-fold lower than that in active RA in cohort 5. In summary, FGL1 is a novel and specific biomarker that could be clinically useful for predicting progression of RA.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1% of the global population [1]
Expressed Proteins in Cohort 1 Are Identified by TMT-Based Proteomics
We found 68 upregulated and 74 downregulated proteins in active RA patients compared to healthy subjects (Figure 2A and Supplementary Table 2)

Summary

INTRODUCTION

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1% of the global population [1]. RA is diagnosed by a total score between six and 10 based on the sum of the individual scores in the four domains in the 2010 Rheumatoid Arthritis Classification Criteria of the American College of Rheumatology/European League Against Rheumatism collaborative initiative [3]. The American College of Rheumatology recommends different treatments for early (disease duration ≤ 6 months) and established (disease duration ≥ 6 months) RA with moderate/high disease activity, with low disease activity and in remission. The disease activity score 28 (DAS28), which is based on the number of tender joint, the number of swollen joint, and the ESR or CRP level, has been widely used for clinical assessment of RA. Cohorts 1– 4 consisted of serum samples from persons with moderate/high active RA, low active RA, RA in remission and healthy subjects. The overall goal was to identify novel biomarkers that could evaluate the disease activity and prognosis of RA (Figure 1)

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT