The prompt identification at the onset of arthritis is difficult to achieve because of the lack of discriminant symptoms or signs and the absence of diagnostic tests1,3. RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance. Subject terms:Rheumatology, Rheumatic diseases, Rheumatoid arthritis == Introduction == The patients with rheumatoid arthritis (RA) should be distinguished from other forms of arthritis for research and clinical management1,2. The prompt identification at the onset of arthritis is difficult to achieve because of the lack of discriminant symptoms or signs and the absence of diagnostic assessments1,3. This limitation has been addressed through the elaboration of classification criteria by the American College of Rheumatology (ACR) and the European League Against Rheumatism, which primary focus is to identify homogeneous groups of patients for research2,4. The current criteria were developed in 2010 2010 to avoid the delay associated with the previous criteria dating from 1987 to permit clinical trials early in the disease course. One of the novelties of the 2010 criteria has been a scoring system that gives a remarkable weight to the best-known RA specific autoantibodies, the rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibodies2. Specifically, the patients showing high levels of any of the two antibodies receive 3 points, whereas the positive patients without high levels receive 2 points. These scores are a large fraction of the 6 points required for RA classification2. These and other changes in the 2010 EULAR/ACR criteria have achieved the intended objective of a Rabbit polyclonal to BNIP2 much prompt classification5,6. However, there is still room for improvement512. Two areas have been identified that could lead to improvements by incorporating new LY-2940094 RA autoantibodies57,1315. The most evident would be if the new antibody could cover the need of a biomarker for the 1545% RA patients that lack RF and anti-CCP antibodies7,13. The accuracy of the current classification criteria for these seronegative patients is much lower than for the patients bearing RF or anti-CCP58,11,12. However, the new RA autoantibodies analysed so far have provided small gains in this area because of their concordance with RF and anti-CCP antibodies1618. It is unclear if this characteristic also applies to the anti-acetylated peptide antibodies (AAPA)18. These antibodies are remarkable in comparison with other new RA autoantibodies1823. Perhaps, they are only comparable in reproducibility and apparent diagnostic characteristics to the anti-carbamylated protein antibodies (anti-CarP)2426, although the two are less sensitive for RA than RF and anti-CCP antibodies. The AAPA are assayed with a modification of the peptide from the mutated citrullinated vimentin (MCV) kit, in which citrulline is LY-2940094 replaced by acetylated lysine (AcLys) or acetylated ornithine (AcOrn)18,19. The test shows low levels of cross-reactivity with anti-CCP and anti-CarP antibodies18. In spite of these promising LY-2940094 clues, the potential value of the AAPA for RA classification has not been fully assessed. The available data shows discrepancies regarding their LY-2940094 sensitivity for the seronegative LY-2940094 patients. On one side, the report where they were first described observed a 13% sensitivity in the anti-CCP unfavorable patients18. Around the other, two meeting abstracts have reported > 40% sensitivity in the seronegative RA patients20,21. These latter results indicate the need to determine if the AAPA could significantly fill the need of a biomarker for the seronegative patients. An alternative area of improvement of the 2010 EULAR/ACR classification criteria will aim to improve their specificity. Particularly, since the 2010 criteria show a loss of specificity relative to the 1987 criteria5,6,10,12. A loss that has been quantified at 4% across 12 studies6. The need for the highest specificity.