Improved classification of rheumatoid arthritis with a score including anti-acetylated ornithine antibodies

Abstract

The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking 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.

Presence of anti-acetylated peptide antibodies (AAPA) in inflammatory arthritis and other rheumatic diseases suggests discriminative diagnostic capacity towards early rheumatoid arthritis

“…Even without the least specific peptide, ac-lysine.inv, the prevalence of AAPA still would be close to 50%. In eRA, the prevalence of individual AAPA ranged from 32% to 39%, which, for ac-lysine, was in reasonable agreement with data from two previous studies, 18 , 33 taking into account that the definition of cut-offs for positivity differed between the three studies. A very recent publication by Rodriguez-Martínez et al demonstrated the value of ac-ornithine implemented in the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria for RA.…”

“… 6 Their data on sensitivity and specificity of AAPA are in good agreement with our results. However, in this study, a high prevalence of AAPA in RF/ACPA negative patients could not be shown, because only ac-lysine and ac-ornithine antibodies were determined, 33 while we found ac-lysine.inv to be the most common antibody in RF/ACPA-negative eRA. Furthermore, in the study of Rodriguez-Martínez et al ., different cut-offs were used for the two assays, whereas we decided to use uniform cut-offs for all three assays, which increased the overall sensitivity of AAPA testing.…”

“…10,18 They were found mostly in ACPA positive patients and partially cross-react with ACPA and/or anti-CarP antibodies. 22,33,34 Nevertheless, AAPA and other AMPAs may also be present in a subgroup of seronegative patients, indicating that they might have added diagnostic value for reducing the serological gap.…”

“… 10 , 18 They were found mostly in ACPA positive patients and partially cross-react with ACPA and/or anti-CarP antibodies. 22 , 33 , 34 Nevertheless, AAPA and other AMPAs may also be present in a subgroup of seronegative patients, indicating that they might have added diagnostic value for reducing the serological gap. In the initial study employing a single acetylated peptide (ac-lysine) and involving only patients with early arthritis they seemed to be less specific than ACPA, but so far this issue has not been thoroughly investigated.…”

Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis

“…Other well established autoantibodies against PTMs also show potential value as biomarkers. For example, the presence of anti-carbamylated protein antibodies or anti-acetylated peptide antibodies can be used to improve RA disease classification [ 15 , 16 ].…”