Algorithm features
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Algorithm 1: plasma Hyp and GSP, G-H1, MG-H1, 3DG-H, CEL, CMA, MetSO, 3-NT, NFK, and DT free adducts
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Algorithm 2: anti-CCP-Ab positivity assessment and plasma GSP, FL, 3DG-H, CML, CEL, MetSO, and 3-NT free adducts
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Classification
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Disease vs control
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eOA vs non-RA and eRA
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eRA vs non-RA and eOA
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Non-RA vs eRA and eOA
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Accuracy (%)
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88.4 (86.9–90.0)
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95.5 (93.7–97.3)
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78.1 (74.3–82.0)
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78.9 (74.7–83.2)
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Sensitivity (%)
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90.4 (88.7–92.1)
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94.0 (88.8–99.3)
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69.1 (54.4–83.7)
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67.5 (46.2–88.8)
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Specificity (%)
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83.2 (77.4–89.0)
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96.1 (92.6–99.6)
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83.2 (71.8–94.6)
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84.6 (77.1–92.1)
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AUROC
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0.93 (0.92–0.94)
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0.98 (0.97–0.99)
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0.86 (0.81–0.90)
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0.88 (0.86–0.90)
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Positive likelihood ratio
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8.26 (5.77–10.75)
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16.11 (9.56–22.66)
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7.66 (2.94–12.37)
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4.96 (3.31–6.60)
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Negative likelihood ratio
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0.11 (0.10–0.13)
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0.06 (0.01–0.11)
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0.34 (0.20–0.48)
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0.36 (0.14–0.57)
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Positive predictive value (%)
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93.6 (91.7–95.6)
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92.8 (86.5–99.0)
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76.3 (65.1–87.4)
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71.8 (62.7–80.8)
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Negative predictive value (%)
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77.3 (74.4–80.2)
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97.5 (95.3–99.6)
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84.4 (79.0–89.8)
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86.2 (78.9–93.4)
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F-score
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0.92 (0.91–0.93)
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0.93 (0.90–0.96)
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0.69 (0.62–0.75)
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0.64 (0.49–0.79)
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- Abbreviations: MetSO Methionine sulfoxide, FL Nε-fructosyl-lysine, G-H1 Glyoxal-derived hydroimidazolone, MG-H1 Methylglyoxal-derived hydroimidazolone, CMA Nω-carboxymethylarginine, 3DG-H 3-Deoxyglucosone-derived hydroimidazolone isomers, GSP Glucosepane, NFK N-formylkynurenine, 3-NT 3-Nitrotyrosine, Hyp Hydroxyproline, eOA Early-stage osteoarthritis, TKR Total knee replacement, RA Rheumatoid arthritis, eRA Early-stage rheumatoid arthritis, DT Dityrosine, CCP Cyclic citrullinated peptide, CML Nε-carboxymethyl-lysine, CEL Nε-carboxyethyl-lysine
- Data are mean (95% CI). Analyte data other than GSP (Table 2) employed in algorithm development were reported previously [5]