Table 2.
Proportions of positivity, and sensitivity and specificity for future rheumatoid arthritis (RA) ofautoantibodies tested at any point in the pre-RA diagnosis period in sero-positive RA cases and controls
| Autoantibody | Case (N=73) | Controls (N=73) | Sensitivity | Specificity (compared to matched military controls) |
Specificity (compared to 200 random blood donor controls**) |
|---|---|---|---|---|---|
| Anti-CCP (>5 units/mL) * | 51 (69.9%) | 0 | 69.9% | 100% | 99.0% |
| RF-IgA (>10.5 units) | 40 (54.8%) | 3 (4.1%) | 54.8% | 95.9% | 98.0% |
| RF-IgG (>10.9 units) | 24 (32.9%) | 5 (6.8%) | 32.9% | 93.2% | 94.0% |
| RF-IgM (>13.6 units) | 41 (56.2%) | 3 (4.1%) | 56.2% | 95.9% | 94.0% |
| Anti-CCP and/or 2 or more RF isotypes | 54 (74.0%) | 1 (1.4%) | 74.0% | 98.6% | 96.5% |
| Sensitivity, specificity of autoantibodies for future RA by pre-diagnosis time interval, and age-at-diagnosis*** |
Anti-CCP | RF-IgA | RF-IgG | RF-IgM | Anti-CCP and/or 2 or more RF isotypes positive |
|---|---|---|---|---|---|
| Time interval ≥0 to ≤1 years prior to RA diagnosis | |||||
| Age-at-diagnosis <40 Sensitivity, Specificity | 77.8%, 100% | 72.2%, 100% | 22.2%, 100% | 55.6%, 100% | 83.3%, 100% |
| Age-at-diagnosis ≥40 Sensitivity, Specificity | 77.8%, 100% | 77.8%, 80.0% | 55.6%, 90.0% | 77.8%, 100% | 77.8%, 90.0% |
| Time interval >1 to ≤5 years prior to RA diagnosis | |||||
| Age-at-diagnosis <40 Sensitivity, Specificity | 61.3%, 100% | 32.3%, 96.8% | 16.1%, 93.6% | 32.3%, 100.0% | 64.5%, 100.0% |
| Age-at-diagnosis ≥40 Sensitivity, Specificity | 64.0%, 100% | 44.0%, 96.0% | 36.0%, 92.0% | 52.0%, 96.0% | 68.0%, 96.0% |
| Time interval >5 to ≤10 years prior to RA diagnosis | |||||
| Age-at-diagnosis <40 Sensitivity, Specificity | 17.6%, 100% | 17.6%, 100.0% | 11.8%, 100.0% | 17.6%, 100% | 23.5%, 100% |
| Age-at-diagnosis ≥40 Sensitivity, Specificity | 43.5%, 100% | 30.4%, 100.0% | 21.7%, 95.6% | 52.2%, 91.3% | 43.5%, 100% |
| Time interval ≥ 10 years prior to RA diagnosis | |||||
| Age-at-diagnosis <40 Sensitivity, Specificity | 0%, 100% | 0%, 100% | 0%, 100% | 0%, 100% | 0%, 100% |
| Age-at-diagnosis ≥40 Sensitivity, Specificity | 18.2%, 100% | 18.2%, 100% | 0%, 100% | 27.3%, 100.0% | 27.3%, 100% |
Of note, if the cut-off for anti-CCP positivity was lowered from >5 units to >2 units, sensitivity and specificity of positivity in any pre-clinical sample for future RA were 75.3% and 100%, respectively, compared to military controls, with a specificity of 96.5% when compared to 200 non-military blood donor controls.
These were random blood donors (N=200, mean age 53, 59% male – not significantly different than military population) and some may have had a diagnosis of RA. As such, specificity using this group as comparison may be underestimated.
Sensitivity, specificity for future RA were calculated in comparison to military controls
RF was also assessed by nephelometry, according to manufacturer’s specifications (Dade Behring, Newark, Delaware, USA), with a cut-off of ≥24.4 units positive yielding a sensitivity and specificity of pre-RA diagnosis positivity for future RA of 53.4 and 93.2%, respectively, when compared to military controls.
Abbreviations: anti-CCP=anti-cyclic citrullinated peptide antibody; RF=rheumatoid factor; Ig=immunoglobulin