Association between markers of inflammation and HRP positivity in FDRs from the Studies of the Aetiology of Rheumatoid Arthritis (SERA) Cohort
| Markers of inflammation | HRP+ FDR visits (n=25)* | HRP− FDR visits (n=81)* | OR† | 95% CI | ||||
|---|---|---|---|---|---|---|---|---|
| Median‡ | Mean‡ | SD‡ | Median‡ | Mean‡ | SD‡ | |||
| hs CRP | 1.15 | 3.19 | 4.11 | 1.93 | 3.33 | 4.21 | 0.91 | 0.56 to 1.47 |
| IL-1β | 1.58 | 1.90 | 1.30 | 1.36 | 1.88 | 3.75 | 1.41 | 0.92 to 2.16 |
| IL-1ra | 80.43 | 93.63 | 46.05 | 71.84 | 95.01 | 98.94 | 1.24 | 0.77 to 1.99 |
| IL-2 | 7.74 | 49.13 | 128.41 | 0.00 | 8.23 | 21.71 | 2.12 | 1.33 to 3.39 |
| IL-4 | 1.34 | 1.36 | 0.48 | 1.02 | 1.55 | 4.23 | 1.60 | 0.99 to 2.60 |
| IL-5 | 1.79 | 2.03 | 0.97 | 1.50 | 3.71 | 14.88 | 1.21 | 0.78 to 1.88 |
| IL-6 | 8.44 | 14.05 | 17.88 | 5.20 | 7.42 | 8.16 | 3.01 | 1.63 to 5.55 |
| IL-7 | 7.14 | 7.94 | 3.40 | 6.00 | 8.57 | 22.69 | 1.53 | 0.97 to 2.43 |
| IL-8 | 12.27 | 12.18 | 4.08 | 11.19 | 12.78 | 6.97 | 1.10 | 0.68 to 1.76 |
| IL-9 | 48.21 | 551.11 | 1080.54 | 18.40 | 39.97 | 71.65 | 2.99 | 1.72 to 5.17 |
| IL-10 | 2.53 | 5.76 | 10.65 | 2.09 | 4.62 | 18.19 | 1.52 | 0.97 to 2.38 |
| IL-12p70 | 16.82 | 118.50 | 485.40 | 16.00 | 20.90 | 33.24 | 1.55 | 0.96 to 2.51 |
| IL-13 | 5.64 | 10.93 | 24.34 | 4.59 | 8.70 | 19.78 | 1.31 | 0.86 to 2.00 |
| IL-15 | 0.00 | 3.29 | 5.99 | 0.00 | 3.03 | 7.88 | 1.21 | 0.77 to 1.90 |
| IL-17 | 13.12 | 13.94 | 10.79 | 8.52 | 11.92 | 12.71 | 1.22 | 0.76 to 1.98 |
| Eotaxin | 78.64 | 91.36 | 41.20 | 78.96 | 90.92 | 51.68 | 1.36 | 0.77 to 2.42 |
| FGF-basic | 57.53 | 66.63 | 56.88 | 40.96 | 63.83 | 138.47 | 1.35 | 0.81 to 2.25 |
| G-CSF | 4.96 | 6.40 | 3.49 | 5.02 | 9.30 | 21.91 | 1.10 | 0.69 to 1.75 |
| GM-CSF | 32.46 | 59.00 | 63.70 | 17.81 | 34.20 | 57.84 | 2.36 | 1.33 to 4.20 |
| IFN-γ | 61.26 | 84.29 | 75.79 | 36.27 | 67.31 | 163.94 | 1.85 | 1.15 to 2.98 |
| IP-10 | 524.92 | 784.51 | 1039.57 | 518.66 | 676.55 | 430.47 | 1.21 | 0.74 to 1.99 |
| MCP-1-MCAF | 35.26 | 57.32 | 48.75 | 40.61 | 58.87 | 52.47 | 1.11 | 0.68 to 1.79 |
| MIP-1α | 4.12 | 5.19 | 5.37 | 4.19 | 5.93 | 12.20 | 0.99 | 0.62 to 1.58 |
| MIP-1β | 105.78 | 111.81 | 43.88 | 99.21 | 110.58 | 51.07 | 1.11 | 0.69 to 1.77 |
| TNF-α | 5.96 | 13.45 | 21.27 | 6.54 | 29.14 | 138.14 | 1.08 | 0.67 to 1.74 |
| VEGF | 81.87 | 106.04 | 99.44 | 59.81 | 83.36 | 78.79 | 1.11 | 0.69 to 1.77 |
| Cytokine Score | 1.56 | 1.68 | 1.01 | 0.44 | 0.53 | 0.57 | 7.67 | 3.23 to 18.19 |
*High Risk Autoantibody Profile (HRP) is defined as positivity for anti-CCP2 and/or two or more RF isotypes, and has been shown in prior work using preclinical RA samples to be >96% specific for future RA.
†All cytokines and chemokines were log-transformed prior to statistical testing. The OR represents the difference in risk associated with a SD increase in hsCRP and the cytokine or chemokine; and a unit increase in the Cytokine Score.
‡We used crude (untransformed) cytokine and chemokine values to calculate the means, SD and median. hsCRP is reported as mg/l and cytokine/chemokine concentrations as pcg/ml.
CRP, C-reactive protein; FDR, first-degree relatives; FGF, fibroblast growth factor; MCAF, monocyte chemotactic and activating factor; MCP, monocyte chemotactic protein; MIP, macrophage inflammatory protein; RA, rheumatoid arthritis; RF, rheumatoid factor; VEGF, vascular endothelial growth factor.