Are antibodies to fine specificities of citrullinated peptides/proteins useful for stratification of rheumatoid arthritis patients?

Background: In rheumatoid arthritis (RA), antibodies to citrullinated protein (ACPA) are believed to be heterogeneous and patient stratification by antibody profiling raised clinical interest for patient management. However, heterogeneity might be partially artificial because of the use of heterogeneous methods for ACPA detection. In recent work instead, we found that ACPA were mainly directed towards a single fibrin-derived peptide, β60-74BiotNt, but a comparative analysis with the presence of other ACPA specificities is still lacking.

Objectives: To present an overview of RA patients' stratification based on the detection of the main ACPA fine specificities with the same method as compared to that of anti-β60-74BiotNt antibodies.

Methods: Over 4500 measurements were performed with more than 22 standardised ELISAs, sera from 180 RA patients and 200 to 436 non-RA rheumatic disease controls.

Results: Four to 81% of RA patients had ACPA towards various targets, confirming the heterogeneity of ACPA specificities. However, the subgroups of patients overlapped up to 97% with ACPA levels of correlation coefficients up to 0.8, showing redundancy of some targets. Multiplexing decreased diagnostic specificity from 95% to 64%. Instead, anti-β60-74BiotNt detection identified almost all ACPA-positive patients.

Conclusions: Antibodies to citrullinated protein multiplexing shows some degree of redundancy and is not suitable for diagnostic purposes. ACPA fine specificities might be less heterogeneous than perceived by sera testing on multiple peptides. Patient stratification largely depends on detection methods and requires standardisation.