Abstract

BackgroundOur previous proteomic study indicated that connective tissue growth factor (CTGF) may be a potential biomarker for rheumatoid arthritis (RA) diagnosis. The aim was to assess the performance of CTGF as a biomarker of RA.MethodSerum and synovial fluid CTGF was detected using a direct high sensitivity sandwich ELISA kit. Serum CTGF levels were tested for discriminatory capacity and optimal assay cutoffs determined in a training cohort of 98 cases of RA with 103 healthy controls. The assay performance was then validated in a further cohort of 572 patients (with RA (n = 217), ankylosing spondylitis (n = 92), gout (n = 74), osteoarthritis (n = 52), systemic lupus erythematosus (n = 72), or primary Sjögren’s syndrome (pSS) (n = 65)).ResultsSignificant elevation of synovial fluid CTGF concentration was found in RA patients, demonstrating excellent diagnostic ability to predict RA (area under the curve (AUC) = 0.97). Similar results were found in serum CTGF detection. At the optimal cutoff value 88.66 pg/mL, the sensitivity, specificity, and the AUC was 0.86, 0.92, and 0.92, respectively, in the training cohort. Similar performance was observed in the validation cohort, with sensitivity, specificity, positive likelihood, and negative likelihood of 0.82, 0.91, 5.74, and 0.12, respectively. Stronger discriminatory capacity was seen with the combination of CTGF and anti-citrullinated protein antibody (ACPA) (AUC = 0.96) than with either ACPA or rheumatoid factor (RF) alone (AUC = 0.80 or 0.79, respectively). The discriminatory performance of serum CTGF was consistent across all inflammatory conditions tested (AUC >0.92 in all cases), with the sole exception of pSS. Serum CTGF did not vary with symptom duration or disease activity.ConclusionsSerum CTGF is a promising diagnostic biomarker for RA, with performance in the current study better than either ACPA or RF.

Highlights

  • Our previous proteomic study indicated that connective tissue growth factor (CTGF) may be a potential biomarker for rheumatoid arthritis (RA) diagnosis

  • Significant elevation of synovial fluid CTGF concentration was found in RA patients, demonstrating excellent diagnostic ability to predict RA (area under the curve (AUC) = 0.97)

  • Stronger discriminatory capacity was seen with the combination of CTGF and anti-citrullinated protein antibody (ACPA) (AUC = 0.96) than with either ACPA or rheumatoid factor (RF) alone (AUC = 0.80 or 0.79, respectively)

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Summary

Introduction

Our previous proteomic study indicated that connective tissue growth factor (CTGF) may be a potential biomarker for rheumatoid arthritis (RA) diagnosis. Yang et al Arthritis Research & Therapy (2017) 19:257 specificity, and RF has relatively higher sensitivity, the current recommendation is to combine RF and ACPA to detect RA. This combination truly improves the diagnostic value of these tests. Studies have found that even the combination of these two markers is not perfect, with sensitivity of 78% and specificity of 82% [5] to detect RF-positive or ACPA-positive patients

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