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Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 2005 December; 64(12): 1731–1736.
Published online 2005 May 5. doi:  10.1136/ard.2005.035691
PMCID: PMC1755298

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis


Background: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria.

Objective: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis.

Methods: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone.

Results: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF [gt-or-equal, slanted]50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF [gt-or-equal, slanted]50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease.

Conclusions: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.

Figure 1
 ROC curve for the tree based model. Using a computer based tree model we obtained the optimum cut off value for RF above which determining anti-CCP and/or anti-RA33 would add no significant benefit in identifying patients with RA. This value ...
Figure 2
 High titre RF and anti-CCP are associated with rapid radiographic progression of RA. Box plots showing the difference in Larsen scores (grade 1 abandoned) in (A) patients with RA with high titre RF v low titre or negative RF; (B) patients with ...
Figure 3
 Prognostic value of autoantibodies for predicting improvement of disease activity. Baseline disease activity (DAS28) was similar in all patient groups (dark grey columns). At the study end point, DAS28 (light grey columns) was significantly ...
Figure 4
 Decision tree to determine risk of RA and erosive disease in patients with early arthritis. All patients with early arthritis are tested for RF. High titre RF ([gt-or-equal, slanted]50 U/ml) is highly predictive for the diagnosis of RA and for developing ...

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