Diagnostic impact of contemporary biomarker assays for rheumatoid arthritis.
OBJECTIVE
The impetus towards early treatment for patients with rheumatoid arthritis (RA) requires more reliable disease markers than the non-specific immunoglobulin M (IgM) rheumatoid factor (RF). To determine the accuracy of newer biomarkers for RA testing for antibody against cyclic citrullinated peptides (anti-CCP Ab), IgA- and IgG-RF and cartilage oligomeric matrix protein (COMP) levels, measured by enzyme-linked immunosorbent assay (ELISA), were compared with IgM-RF isotyping.


METHODS
Serum samples were investigated in patients with an established diagnosis of RA (n = 54), ankylosing spondylitis (AS) (n = 36), and non-inflammatory conditions (n = 18) (cohort A), and in 234 consecutive outpatients in a blinded fashion (cohort B). Non-parametric analysis of areas under the curve (AUC) of receiver operator characteristics were performed.


RESULTS
The presence of anti-CCP Ab had the highest accuracy (96%) in distinguishing RA patients in cohort A and cohort B (accuracy 83%), and in both cohorts combined (accuracy 87%). This was related to the high specificity of anti-CCP Ab for RA (95-96%), even though IgM-RF was the most sensitive test (87-96%). Sensitivity (15-48%) and specificity (66-69%) of COMP as a marker for RA was low. Combining results of anti-CCP Ab and IgM-RF or any of the other assays did not increase the diagnostic accuracy for RA.


CONCLUSIONS
The presence of anti-CCP Ab is the most accurate biomarker for RA in both selected and unselected cohorts, while the COMP assay is not very useful in RA diagnosis. Combining assays for anti-CCP Ab and IgM-RF or IgA-RF does not enhance RA diagnosis.
Nikolaisen
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Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Tromsø. Norway. cathrin.nikolaisen@unn.no
Rekvig
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OP
Nossent
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HC
D000368:Aged; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007159:Immunologic Tests / Q000295:instrumentation; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood / Q000145:classification*; D012680:Sensitivity and Specificity
D000906:Antibodies; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D010456:Peptides, Cyclic; C577553:TSP5 protein, human; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor