Rheumatoid arthritis

The determination of ACPA has been part of the RA classification criteria of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) since 2010. ACPA are determined in parallel to RF. According to the scoring system of the ACR/EULAR classification, a high ACPA or RF titer carries more weight for the classification of RA than a lower titer. Laboratory findings such as an increased erythrocyte sedimentation rate, increased C-reactive protein and the presence of RF and/or ACPA are indicative of RA Aletaha et al., Ann Rheum Dis (2010), 69:1580-1588).

Autoantibodies against CCP can be determined using ELISA and ChLIA. For the detection of ACPA, the second-generation CCP antigen (CCP2) is considered the gold standard. Test systems based on this antigen provide the highest sensitivity (80 %, with a specificity of 98%). Antibodies against CCP are mainly IgG class antibodies and are significantly more specific than RF, with a similar sensitivity. Anti-CCP antibodies are found in up to 60 % of RF-negative patients.

CEP-1 is another relevant autoantigen, which is present in approx. 60 % of anti-CCP-positive RA patients. The detection of antibodies against CEP-1 is highly specific for RA (specificity: 97.6 %) and therefore suited as a supplementary test for the confirmation of serological findings. Moreover, the detection of anti-CEP-1 supports risk stratification: Anti-CEP-1 antibodies are associated with an erosive disease course and with interstitial lung disease (Alunno et al., Rheumatology (2018) 57:850-855). Furthermore, anti-CEP-1 antibodies occur in a subtype of RA for which smoking and the HLA-DRB1 “shared epitope” alleles are the main risk factors (Mahdi et al., Nat Genet (2009) 41:1319-1324). Since anti-CEP-1 antibodies are directed against a target antigen which actually occurs in RA, their detection can provide insight into the cause and the pathogenesis of the disease.