Value of antibodies against acetylated peptides for the classification of patients with early arthritis

Abstract

Methods: A total of 438 patients with available samples and information were randomly selected from two early arthritis clinics. The AAPA were determined in baseline sera as previously described (1). Two peptides were included, one acetylated at a lysine (anti-AcLys) and the other at an ornithine (anti-AcOrn) and considered either individually or combined. The sensitivity, specificity, predictive positive (PPV) and negative (PNV) values and the AUC of the ROC curve were assessed. Logistic regression was also applied adjusting for age, sex, the centre of origin, anti-CCP, and RF. The study was approved by the ethics committee of the Hospital Universitario La Paz, the Hospital Universitario La Princesa, and Autonómico de Galicia.

Results: The AAPA at baseline were sensitive and specific for the classification of the patients fulfilling RA criteria (46.8%) at the end of the 2-year follow-up (table 1). Specifically, the anti-AcOrn antibodies were slightly more sensitive and specific than the anti-AcLys ones. The two and their combination showed a conserved specificity for the seronegative patients, but a lower sensitivity than for the seropositive ones. Consequently, the PPV for the seronegative patients was low, although the NPV was high. In the same vein, the AUC was insufficient for the seronegative patients. The regression analysis including the anti-CCP and RF revealed a significant contribution of the anti-AcOrn antibodies (OR = 2.1, 95% CI = 1.1 – 4.0, P = 0.02), but not of the anti-AcLys antibodies. On the other hand, the inclusion of the AAPA in the classification resulted in an increase in sensitivity of 5.4% at the cost of a 13.7% lower specificity, which is an improvement over the anti-carbamylated protein antibodies.

Conclusion: The AAPA show high specificity and sensitivity for RA in early arthritis patients. However, their contribution to RA classification is minor once RF and the anti-CCP antibodies have been considered. But nevertheless, AAPA supports the drive to close the diagnostic gap in this early disease phase and to increase the likelihood of successful therapy.