Citrullinated Peptides as a Substrate for the Detection of Rheumatoid Arthritis-Specific Autoantibodies

The diagnosis of rheumatoid arthritis (RA) depends primarily on the clinical manifestation of the disease. The only serologic test routinely used is the determination of the presence of rheumatoid factors in the serum. However, these antibodies are also present in relatively high percentages in other autoimmune and infectious diseases and in up to 15% of healthy individuals. Antibodies of a more specific nature were first described by Nienhuis and Mandema [1], who discovered that RA sera specifically label the 'perinuclear factor', a component of the keratohyaline granules in buccal mucosa cells. These antiperinuclear factor (APF) antibodies are reported to be present in 49–91% of RA patients, with a specificity of over 70%. Due to technical reasons, the APF test never became very popular.

We discovered that APF-directed autoantibodies in RA specifically recognise citrullinated residues in polypeptides [3] and developed an ELISA procedure using a single cyclic citrullinated peptide (CCP) as substrate. Our studies showed that the anti-CCP ELISA assay was positive in about 70% of RA sera, with a specificity of more than 98% against disease controls (n > 700). Other studies, which will be presented, corroborate the extreme diagnostic specificity of this auto-antibody for RA. Therefore, we expect that a serologic test based on our peptides will be a valuable addition to RA diagnostics and a help in the decisions to be made concerning the treatment of early RA patients.