Urinary Proteome Profile Predictive of Disease Activity in Rheumatoid Arthritis

Kang, Min Jueng; Joo, Young Bin; You, Sungyong; Yoo, Sehoon; Choi, Susanna; Kim, Dongho; Cho, Chul-Soo; Yi, Eugene C.; Hwang, Daehee; Kim, Wan‐Uk

doi:10.1021/pr500467d

Cited by 31 publications

(30 citation statements)

References 54 publications

(86 reference statements)

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“…Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (ACPA) are representative serological markers for RA diagnosis and prognosis, including radiographic progression, but they do not usually correlate with disease progression ( 10 ). Urine soluble CD14 was reported to be a biomarker of high disease activity of RA, but the area under the receiver operating characteristic (ROC) curve was only 0.71 ( 11 ). 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.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Guo

et al. 2020

Front. Immunol.

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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.

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Section: Introductionmentioning

confidence: 99%

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

Liu

Guo

et al. 2020

Front. Immunol.

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“…For many diseases, urine can be used to provide complementary information to that collected via serum measures 7 8 9 . Some urinary chemokines including chemokine (C-C motif) ligand 2 (CCL2) from SLE patients can be potential biomarkers for detecting preclinical renal damage and monitoring renal flares 7 .…”

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confidence: 99%

“…Urinary collagen fragments also may be useful for early diagnosis of diabetic nephropathy 8 . Previously, we performed quantitative proteome profiling of urine samples from RA patients and non-RA controls using liquid chromatography−tandem mass spectrometry (LC−MS/MS) analysis 9 . Through integrative analysis with transcriptomes of synovial tissues, we demonstrated that proteomic signatures in the urine of RA patients reflect inflammation-related cellular processes, including cell adhesion, immune response, and proteolysis.…”

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confidence: 99%

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation

Joo

Yoo

Kım

et al. 2016

Sci Rep

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Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

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“…Previously, Kang et al performed quantitative urinary proteome profiling of urine samples from RA and osteoarthritis (OA) patients using a label-free LC-MS/MS analysis ( 42 ). Using these urinary protein profiles, they identified 134 DEPs between RA and OA urine samples.…”

Section: Exploration Of Novel Biomarkers Using a Proteomic Approachmentioning

confidence: 99%

Proteomics in Rheumatoid Arthritis Research

et al. 2015

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Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the large-scale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets.

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Urinary Proteome Profile Predictive of Disease Activity in Rheumatoid Arthritis

Cited by 31 publications

References 54 publications

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

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

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation

Proteomics in Rheumatoid Arthritis Research

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