Something old, something new: biomarkers in rheumatoid arthritis

The detection of RA in its early stages is often challenging, and the measurement of ACPA levels is crucial. Given the specificity of ACPA for RA, a positive result in any assay has a high predictive value for diagnosis; 40% positivity has been reported using the cyclic citrullinated peptide (CCP) assay and similar or slightly lower percentages by other assays. Unfortunately, with all the assays now available, the frequency of a positive result is lower in early RA — when treatment would be most efficacious — than in later disease. A small increment in the frequency of positive results may be obtained by conducting parallel assays using different citrullinated substrates. In fact, the overlap of the CCP assay with the other tests for ACPA is not complete: sera that are anti-CCP-negative, but positive for antiviral citrullinated peptide, anticitrullinated fibrinogen, or anti-modified citrullinated vimentin antibodies do exist, and have been reported in 2%–7% of tested RA populations. In the future, the diagnosis of RA could benefit greatly from the gathering of information through the assaying of many variables simultaneously — for example, a cluster of biomarkers associated with genotyping — leading to the more accurate prediction of disease outcome and to more effective, individualized treatment.