Table 3.
Positivity of cytokines/chemokines and C-reactive protein in at least one sample at any time prior-to-diagnosis of rheumatoid arthritis (RA), and sensitivity and specificity for future sero-positive rheumatoid arthritis (RA), in sero-positive RA cases (N=73) and matched controls*
| Biomarker | Cases, N (%) | Controls, N (%) | P-value | Sensitivity (%)** | Specificity (%)** |
|---|---|---|---|---|---|
| Eotaxin | 10 (13.7) | 12 (16.4) | 0.64 | 13.7 | 86.3 |
| FGF2 | 28 (38.4) | 12 (16.4) | <0.01 | 38.4 | 83.6 |
| FLT3-Ligand | 42 (57.5) | 29 (39.7) | 0.03 | 57.5 | 60.3 |
| GMCSF | 33 (45.2) | 15 (20.6) | <0.01 | 45.2 | 53.4 |
| IL1α | 39(53.4) | 26(35.6) | 0.03 | 53.4 | 64.4 |
| IL1β | 28 (38.4) | 15 (20.6) | 0.02 | 38.4 | 79.4 |
| IL6 | 25 (34.2) | 14 (19.2) | 0.04 | 34.2 | 80.8 |
| IL10 | 27 (37.0) | 11 (15.0) | <0.01 | 37.0 | 84.9 |
| IL12P40 | 41 (56.2) | 17 (23.3) | <0.01 | 56.2 | 76.7 |
| IL12P70 | 29 (39.7) | 17 (23.3) | 0.03 | 39.7 | 76.7 |
| IL15 | 31 (42.5) | 13 (17.8) | <0.01 | 42.5 | 82.2 |
| IP10 | 41 (56.2) | 25 (34.2) | 0.01 | 56.2 | 65.8 |
| MCP1 | 27 (37.0) | 24 (32.9) | 0.60 | 37.0 | 67.1 |
| TNFα | 33 (45.2) | 14 (19.2) | <0.01 | 45.2 | 80.8 |
| Sensitivity/Specificity of cytokine/chemokine counts in combination with autoantibodies (in any pre-RA diagnosis sample) for future seropositive rheumatoid arthritis (cases N=73) | |||||
|---|---|---|---|---|---|
| Biomarkers | Cases, N (%) | Controls N (%) | P-value | Sensitivity(%)** | Specificity(%)** |
| >5 cytokines/chemokines (any type) | 29 (39.7) | 16 (21.9) | 0.02 | 39.7 | 78.1 |
| >10 cytokines/chemokines (any type) | 12 (16.4) | 3 (4.1) | 0.03 | 16.4 | 95.9 |
| Anti-CCP | 51 (69.9) | 0 (0) | <0.01 | 69.9 | 100 |
| Anti-CCP and/or >5 cytokines/chemokines | 57 (78.1) | 16 (21.9) | <0.01 | 78.1 | 78.1 |
| Anti-CCP and/or >10 cytokines/chemokines | 53 (72.6) | 3 (4.1) | <0.01 | 72.6 | 95.9 |
| Any sample with single RF isotype (any) positive | 11 (15.1) | 9 (12.3) | 0.81 | 15.1 | 87.7 |
| Single RF isotype and/or >5 cytokines/chemokines | 39 (53.4) | 21 (28.8) | <0.01 | 53.4 | 71.2 |
| Single RF isotype AND >5 cytokines/chemokines | 1 (1.4) | 4 (5.5) | 0.34 | 1.4 | 94.5 |
| Single RF isotype and/or >10 cytokines/chemokines | 23 (31.5) | 10 (13.7) | 0.02 | 31.5 | 86.3 |
| Single RF isotype AND >10 cytokines/chemokines | 0 (0) | 2 (2.7) | 0.5 | 0.0 | 97.3 |
| Anti-CCP and/or 2 or more RF isotypes | 54 (74.0) | 1 (1.4) | <0.01 | 74.0 | 98.6 |
| Anti-CCP and/or ≥ 2 RF isotypes and/or >5 cytokines/chemokines | 59 (80.8) | 17 (23.3) | <0.01 | 80.8 | 76.7 |
| Anti-CCP and/or ≥ 2 RF isotypes AND >5 cytokines/chemokines | 24 (32.9) | 0 (0) | <0.01 | 32.9 | 100 |
| Anti-CCP and/or 2 or more RF isotypes and/or >10 cytokines/chemokines | 55 (75.3) | 4 (5.5) | <0.01 | 74.3 | 94.5 |
| Anti-CCP and/or 2 or more RF isotypes AND >10 cytokines/chemokines | 11 (15.1) | 0 (0) | <0.01 | 15.1 | 100 |
Cases are individuals who developed seropositive RA (RF and/or anti-CCP positive); controls are military subjects without RA, matched to cases on age, race, gender and duration of serum sample storage.
Sensitivity/specificity for future seropositive RA, in case-control analysis
Abbreviations: RF=rheumatoid factor (isotypes IgG, IgM, IgA); anti-CCP= anti-cyclic citrullinated peptide antibody; interleukin (IL)-1α, IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, Eotaxin ( or CCL11), fibroblast growth factor-2 (FGF-2), Flt-3 ligand, tumor necrosis factor-α (TNF-α), interferon gamma induced protein-10 (IP-10)( or CXCL10), granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemotactic protein-1 (MCP-1) (or CCL-2); cytos/chemos=cytokines/chemokines