Background/Purpose:

Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are important serological markers in the diagnosis of rheumatoid arthritis (RA) and are part of the recent disease criteria. However, in early RA the sensitivities of ACPA and RF are low underlining the need for additional biomarkers. Additionally, there is a strong need for reliable markers for monitoring of disease activity and treatment response. Recently, antibodies directed against carbamylated antigens were identified. Those anti-CarP antibodies recognize antigens containing homocitrulline which is generated from lysine through chemical modification. This study analyzes the correlation of ACPA fine specificities and of anti-CarP antibodies with disease activity and disease duration.

Methods:

A total of 80 RA patients were tested for anti-CCP2 (CCPlus® Immunoscan, Eurodiagnostica) and anti-CCP3 antibodies (QUANTA Lite CCP3, INOVA), for ACPA fine specificities (to three citrullinated peptides, ACPA 1 – 3) and for anti-CarP antibodies by ELISA using fetal calf serum as the antigen as previously described (Shi et al.). In addition RF (IgM) was determined. Disease activity was accessed using the disease activity score 28 (DAS28).

Results:

ACPA, including anti-CCP2 (p=0.0050) and anti-CCP3 (p=0.0128) antibodies, as well as the ACPA fine specificities showed significant association with disease duration. In contrast, RF and anti-CarP antibodies did not show association with disease duration. Although no correlation between any of the autoantibodies and disease activity (DAS28) reached statistical significance, one ACPA peptide showed some degree of positive (p=0.0734) and anti-CarP antibodies negative correlation (p=0.0734). When those two biomarkers were combined in a score (ACPA peptide 1 divided by anti-CarP) a statistically relevant correlation was found (p=0.0264).

Conclusion:

We confirmed the presence of anti-CarP antibodies in RA using an independent cohort of RA patients from Italy. ACPA, but not RF IgM and anti-CarP antibodies are significantly correlated with disease duration. Combining one ACPA peptide with anti-CarP antibodies in an activity score showed association with DAS28. This score might represent a promising biomarker to measure disease activity, but further studies are needed to verify and validate those preliminary findings.