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 >or=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 >or=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.
Nell
V P K
VP
Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Austria.
Machold
K P
KP
Stamm
T A
TA
Eberl
G
G
Heinzl
H
H
Uffmann
M
M
Smolen
J S
JS
Steiner
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000000981:diagnostic imaging; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D042241:Early Diagnosis; D004812:Epidemiologic Methods; D006801:Humans; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood; D012261:Ribonucleoproteins / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; D012261:Ribonucleoproteins; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor