Table 4.
Proportions of samples from seropositive rheumatoid arthritis (RA) cases (N=73) positive for biomarkers during defined pre-diagnosis time intervals, by age-at-diagnosis grouping*
| Age-at-diagnosis of RA <40 | Age-at-diagnosis of RA ≥40 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervals prior to diagnosis (in years) |
≥10 | <10≥5 | <5≥1 | <1≥0.5 | <0.5≥0 | Samples (cases)** |
≥10 | <10≥5 | <5≥1 | <1≥0.5 | <0.5≥0 | Samples (cases)** |
| Anti-CCP | 0.00 (0) | 0.08 (3) | 0.53 (19) | 0.22 (8) | 0.17 (6) | 36 (26) | 0.06 (2) | 0.29 (10) | 0.46 (16) | 0.08 (3) | 0.14 (5) | 35 (25) |
| RF-IgA | 0.00 (0) | 0.12 (3) | 0.38 (10) | 0.23 (6) | 0.27 (7) | 26 (20) | 0.07 (2) | 0.23 ( 7) | 0.41 (11) | 0.11 (3) | 0.18 (5) | 27 (20) |
| Rf-IgG | 0.00 (0) | 0.18 (2) | 0.46 ( 5) | 0.00 (0) | 0.36 (4) | 11 (9) | 0.00 (0) | 0.26 ( 5) | 0.47 ( 9) | 0.15 (3) | 0.15 (3) | 19 (15) |
| RF-IgM | 0.00 (0) | 0.13 (3) | 0.44 (10) | 0.17 (4) | 0.26 (6) | 23 (18) | 0.08 (3) | 0.34 (12) | 0.37 (13) | 0.08 (3) | 0.14 (5) | 35 (23) |
| High Risk*** | 0.00 (0) | 0.10 (4) | 0.51 (20) | 0.20 (8) | 0.18 (7) | 39 (27) | 0.08 (3) | 0.27 (10) | 0.46 (17) | 0.08 (3) | 0.14 (5) | 37 (27) |
| Eotaxin | 0.00 (0) | 0.17 (1) | 0.33 (2) | 0.17 (1) | 0.33 (2) | 6 (5) | 0.00 (0) | 0.80 (4) | 0.20 (1) | 0.00 (0) | 0.00 (0) | 5 (5) |
| FGF2 | 0.00 (0) | 0.19 (4) | 0.52 (11) | 0.10 (2) | 0.19 (4) | 21 (17) | 0.00 (0) | 0.31 (4) | 0.38 (5) | 0.14 (2) | 0.21 (3) | 13 (11) |
| FLT3 | 0.07 (2) | 0.15 (4) | 0.52 (14) | 0.11 (3) | 0.15 (4) | 27 (22) | 0.00 (0) | 0.46 (11) | 0.42 (10) | 0.04 (1) | 0.08 (2) | 24 (20) |
| GMCSF | 0.11 (3) | 0.18 (5) | 0.41 (11) | 0.11 (3) | 0.19 (5) | 27 (20) | 0.6 (1) | 0.35 (6) | 0.53 (9) | 0.00 (0) | 0.06 (1) | 17 (13) |
| IL1α | 0.08 (2) | 0.08 (2) | 0.54 (14) | 0.12 (3) | 0.19 (5) | 26 (17) | 0.03 (1) | 0.38 (11) | 0.41 (12) | 0.07 (2) | 0.10 (3) | 29 (22) |
| IL1β | 0.00 (0) | 0.11 (2) | 0.50 (9) | 0.17 (3) | 0.22 (4) | 18 (15) | 0.00 (0) | 0.41 (7) | 0.29 (5) | 0.06 (1) | 0.23 (4) | 17 (13) |
| IL6 | 0.00 (0) | 0.07 (1) | 0.47 (7) | 0.20 (3) | 0.27 (4) | 15 (13) | 0.07 (1) | 0.40 (6) | 0.40 (6) | 0.07 (1) | 0.07 (1) | 15 (12) |
| IL10 | 0.10 (2) | 0.15 (3) | 0.50 (10) | 0.05 (1) | 0.20 (4) | 20 (18) | 0.10 (1) | 0.40 (4) | 0.50 (5) | 0.00 (0) | 0.00 (0) | 10 (9) |
| IL12P40 | 0.07 (2) | 0.11 (3) | 0.59 (16) | 0.07 (2) | 0.15 (4) | 27 (21) | 0.04 (1) | 0.36 (10) | 0.46 (13) | 0.07 (2) | 0.10 (3) | 28 (20) |
| IL12P70 | 0.10 (2) | 0.10 (2) | 0.47 (9) | 0.11 (2) | 0.21 (4) | 19 (16) | 0.00 (0) | 0.38 (5) | 0.54 (7) | 0.00 (0) | 0.08 (1) | 13 (13) |
| IL15 | 0.04 (1) | 0.18 (4) | 0.50 (11) | 0.04 (1) | 0.23 (5) | 22 (18) | 0.00 (0) | 0.27 (4) | 0.47 (7) | 0.19 (3) | 0.12 (2) | 15 (13) |
| IP10 | 0.00 (0) | 0.12 (3) | 0.63 (15) | 0.04 (1) | 0.21 (5) | 27 (19) | 0.11 (3) | 0.38 (10) | 0.38 (10) | 0.04 (1) | 0.08 (2) | 26 (22) |
| MCP | 0.00 (0) | 0.24 (4) | 0.47 (8) | 0.06 (1) | 0.23 (4) | 17 (13) | 0.17 (3) | 0.39 (7) | 0.33 (6) | 0.00 (0) | 0.11 (2) | 18 (14) |
| TNFα | 0.00 (0) | 0.19 (4) | 0.48 (10) | 0.09 (2) | 0.24 (5) | 21 (17) | 0.10 (2) | 0.47 (9) | 0.31 (6) | 0.05 (1) | 0.10 (2) | 19 (16) |
| CRP>5 | 0.00 (0) | 0.07 (1) | 0.36 (5) | 0.285 (4) | 0.285 (4) | 14 (13) | 0.09 (2) | 0.32 (7) | 0.41 (9) | 0.04 (1) | 0.14 (3) | 22 (16) |
| CRP>10 | 0.00 (0) | 0.12 (1) | 0.12 (1) | 0.375 (3) | 0.375 (3) | 8 (8) | 0.00 (0) | 0.50 (4) | 0.38 (3) | 0.00 (0) | 0.12 (1) | 8 (8) |
| 0-4 positive**** | 0.09 (4) | 0.28(13) | 0.39 (18) | 0.13 (6) | 0.11 (5) | 46 (26) | 0.22(11) | 0.32 (16) | 0.36 (18) | 0.02 (1) | 0.08 (4) | 50 (33) |
| 5-9 positive**** | 0.08 (1) | 0.23 (3) | 0.54 (7) | 0.15 (2) | 0.00 (0) | 13 (12) | 0.00 (0) | 0.22 (2) | 0.44 (4) | 0.20 (2) | 0.20 (2) | 9 (9) |
| 10+ positive**** | 0.00 (0) | 0.08 (1) | 0.50 (6) | 0.09 (1) | 0.33 (4) | 12 (11) | 0.00 (0) | 0.56 (5) | 0.33 (3) | 0.00 (0) | 0.11 (1) | 9 (9) |
| Cases (samples) for each interval |
5 (5) | 17 (27) | 31 (56) | 9 (9) | 9 (9) | 11 (14) | 23 (40) | 25 (42) | 3 (3) | 7 (7) | ||
- Time period ≥10 years prior-to-diagnosis, <40 median count 0.5; ≥40 median count 1.0; p=0.43
- Time period <10 to ≥5 years prior-to-diagnosis, <40 median count 3.0; ≥40 median count 6.5, p<0.01
- Time period <5 to ≥1 years prior-to-diagnosis, <40 median count 10.5; ≥40 median count 6.5, p=0.01
- Time period <1 to ≥0 years prior-to-diagnosis (combined samples ≤1 year prior-to-diagnosis), <40 median count 6.0; ≥40 median count 3.0, p<0.01
In rows, the initial number X in each column represents the proportion of samples during that interval that was positive for the given biomarkers; the following number (in parentheses) represents the raw number of samples that were positive during this interval. The proportion of samples positive is calculated by dividing the number of samples positive by the total number of samples positive for each biomarker, which is listed in the final column for each age-at-diagnosis group.
In these columns, these numbers X(X) represent, respectively, the total number of samples that were positive for each biomarker during the entire pre-clinical RA period, and the number of cases that were positive for this biomarker at any point in the pre-diagnosis period.
High risk = Anti-CCP and/or 2 or more RF isotypes, positivity for which in any pre-clinical sample is 74% sensitive and >96% specific for future RA
These values are ranges of numbers of cytokines/chemokines that were positive
Abbreviations: Anti-CCP=anti-cyclic citrullinated peptide antibody; RF=rheumatoid factor; Ig=immunoglobulin; high-risk = anti-CCP and/or 2 or more RF isotypes positive (>96% specific for future sero-positive RA); 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); CRP=C-reactive protein