Abstract
Aims:To determine the diagnostic value of anti-acetylated peptide antibodies (AAPA) in patients with rheumatoid arthritis (RA).Methods:Three acetylated peptides (ac-lysine, ac-lysine.inv and ac-ornithine) derived from vimentin were employed to measure AAPA by enzyme-linked immunosorbent assay (ELISA) in sera of 120 patients with early RA (eRA), 195 patients with established RA (est RA), 99 healthy controls (HC), and 216 patients with other inflammatory rheumatic diseases. A carbamylated and a citrullinated version of the vimentin peptide were used additionally. Receiver operating characteristics and logistic regression analyses were used to assess the discriminative capacity of AAPA.Results:AAPA were detected in 60% of eRA and 68.7% of estRA patients, 22.2% of HC, and 7.1– 30.6% of patients with other rheumatic diseases. Importantly, AAPA were also present in 40% of seronegative RA patients, while antibodies to the carbamylated peptide were detected less frequently. Diagnostic sensitivity of individual peptides for eRA was 28.3%, 35.8%, and 34% for ac-lysine, ac-ornithine, and ac-lysine.inv, respectively. Positive likelihood ratios (LR+) for eRA versus HC were 14.0, 7.1, and 2.1. While the presence of a single AAPA showed varying specificity (range: 84–98%), the presence of two AAPA increased specificity considerably since 26.7% of eRA, as compared with 6% of disease controls, were double positive. Thus, double positivity discriminated eRA from axial spondyloarthritis with a LR+ of 18.3. Remarkably, triple positivity was 100% specific for RA, being observed in 10% of eRA and 21.5% of estRA patients, even in the absence of RF and ACPA.Conclusion:AAPA are highly prevalent in early RA and occur also independently of RF and ACPA, thereby reducing the gap of seronegativity. Furthermore, multiple AAPA reactivity increased the specificity for RA, suggesting high diagnostic value of AAPA testing.
Highlights
Diagnostic performance of acetylated peptide antibodies (AAPA) testing in patients with rheumatoid arthritis (RA) To establish the diagnostic value of AAPA in patients with early RA (eRA), sera from 99 healthy donors and 120 eRA patients (75% female) with a median symptom duration of 0.7 [interquartile range (IQR): 0.3–1.9] years and a median SDAI
Among the eRA patients, 50% were positive for anti-citrullinated-peptide antibodies (ACPA) and 53.3% for rheumatoid factor (RF), with 46% being positive for both antibodies
Currently only RF and ACPA are used in routine diagnostics because the added diagnostic value of the other anti-modified protein autoantibody (AMPA) is still uncertain and commercial assays are not yet available
Summary
Study design and patients All samples used in this study had been previously acquired and stored in the biobank (biological specimen registry) of the Medical University of Vienna (EC-Number: 559/2005),[24] and all patients had provided written informed consent, which follows the rules of the declaration of Helsinki and was approved by the Ethics Committee of the Medical University Vienna.[25]. To assess the precision of the AAPA ELISA, low (L), medium (M) and high (H) value samples were assayed in five independent tests on 1 day (inter-assay) or in a single run (intra-assay). The cut-off for positivity was determined by receiver operating characteristic (ROC) curve analysis as described . Statistical analyses Descriptive statistics on antibody levels in all cohorts and clinical and descriptive variables of eRA and estRA have been generated. ROC curves using antibodies (abs) against ac-lysine, ac-lysine.inv, and ac-ornithine were generated by testing eRA and estRA versus healthy subjects to evaluate a cut-off for positivity of AAPA. By means of linear regression non-parametric tests and correlation analyses, we evaluated differences in clinical characteristics depending on AAPA positivity and titer. All analyses were performed using SPSS version 25, Medcalc and STATA
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