ABSTRACT
BACKGROUND: Our 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. METHOD: Serum 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)). RESULTS: 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). 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. CONCLUSIONS: Serum CTGF is a promising diagnostic biomarker for RA, with performance in the current study better than either ACPA or RF.
Subject(s)
Arthritis, Rheumatoid/blood , Biomarkers/blood , Connective Tissue Growth Factor/blood , Synovial Fluid/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/diagnosis , Cohort Studies , Diagnosis, Differential , Female , Gout/blood , Gout/diagnosis , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Osteoarthritis/blood , Osteoarthritis/diagnosis , Sensitivity and Specificity , Sjogren's Syndrome/blood , Sjogren's Syndrome/diagnosis , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/diagnosis , Young AdultABSTRACT
To identify special metabolites in synovial fluid of osteoarthritis (OA) via a metabolomics approach. Synovial fluid of 35 participants (25 OA patients and 10 controls) was detected by GC-TOF/MS and multivariate data analysis was applied to analyze correlation among the observations. Different metabolites were screened by VIP value (VIP > 1), student t-test (p < 0.05), and fold change (fold >1.5), and verified with the standard metabolites in the synovial fluid of 24 OA patients and 11 controls by LC/MS. The classification performance of different metabolites was analyzed by receiver operating characteristic (ROC) analysis. The results showed that six different metabolites (glutamine, 1,5-anhydroglucitol, gluconic lactone, tyramine, threonine, and 8-aminocaprylic acid) were strongly associated with OA in global metabolomics. Verified results of the first three metabolites were the same as the identified results using targeted metabolomics. ROC curve analysis demonstrated that their concentrations in synovial fluid were strongly correlated to OA. In addition, the concentrations of gluconic lactone were significantly different between OA and RA. Metabolites with altered levels may be contributors to OA pathogenesis and can be used as potential diagnosis criteria for OA. Gluconic lactone may prove to be a novel criterion for differential diagnosis of OA from RA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1973-1981, 2017.
