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

Lorena Rodriguez-Martínez,Diana Peiteado,Cristina Regueiro,Ana M Ortiz,Ana Triguero-Martinez,Isidoro Gonzalez-Alvaro,Alejandro Balsa,Alejandro Villalba,Holger Bang,Laura Nuño,Ana Martinez-Feito,Antonio Gonzalez

doi:10.1038/s41598-020-73919-y

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.

Highlights

The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria
The acetylated peptide antibodies (AAPA) are assayed with a modification of the peptide from the mutated citrullinated vimentin (MCV) kit, in which citrulline is replaced by acetylated lysine (AcLys) or acetylated ornithine (AcOrn)[18,19]
All the studies showed the three antibodies were much more concordant in the RA patients than in the controls, either healthy controls, first degree relatives of RA patients, or disease controls[24]. This characteristic was exploited by us to replace the serological component of the American College of Rheumatology (ACR)/EULAR 2010 classification criteria by a score based on the concordance of the anti-CarP, RF and anti-CCP autoantibodies

Summary

Introduction

The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. All the studies showed the three antibodies were much more concordant in the RA patients than in the controls, either healthy controls, first degree relatives of RA patients, or disease controls[24] This characteristic was exploited by us to replace the serological component of the ACR/EULAR 2010 classification criteria by a score based on the concordance of the anti-CarP, RF and anti-CCP autoantibodies. This score led to classify the patients with similar accuracy in our c ohort[14], and, independently in another large cohort of patients with E A15. Antibody concentrations vary between laboratories and it has been shown to limit reproducibility of the RA classification criteria[10]

Methods

Results

Conclusion