SAT0065 Acpa against different citrullinated peptides identify specific phenotypes of rheumatoid arthritis
Authors: M Brink, M Hansson, L Mathson-Alm, M Cornillet, J Rönnelid, K Skriner, G Serre, R Holmdahl, L Klareskog, S Rantapää-Dahlqvist
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anti-citrullinated protein/peptide antibodies (ACPA) have been suggested to identify a more severe phenotype of rheumatoid arthritis (RA). <h3>Objectives</h3> In this study in an inception cohort of early RA we have analysed a number of antibodies against different citrullinated and/or mutated peptides using a multiplex platform in relation to the patients disease inflammation and radiological destruction <h3>Methods</h3> Patients with early RA (≤12 m of symptoms) fulfilling the 1987 ARA criteria (n=1022, 692f/330m, mean age56.7±14.0 years) were sampled at the time of diagnosis and assessed using disease activity score (DAS28) at baseline, 6, 12, 18 and 24 months. Radiographs were graded using Larsen score (baseline and <i>at</i> 24 m). Plasma sampled at baseline was analysed for presence of antibody reactivities against 21 different citrullinated peptides/proteins; Fibrinogen (Fib) α36–50, Fibα573, Fibα591, Fibα621–635, Fibβ36–52, Fibβ60–74, Fibβ62–78 (72), Fibβ62–78 (74), Filaggrin (Fil307–324), α-Enolase peptide 5–21 (CEP-1), Vimentin (Vim) 2–17, Vim60–75, F4-R-Cit, F4-Cit-Cit, F4- Cit-R), or mutated proteins (Bla26, Pept1, Pept5, PeptZ1, PeptZ2) and type II Collagen citrullinated or not using a custom-made microarray assay based on the ImmunoCAP ISAC system (Phadia AB, Sweden). Cut-off levels were at the 98th percentile of controls (n=477). Anti-CCP2 was analysed using ELISA (Euro Diagnostica, Sweden). <h3>Results</h3> The most frequent appearing ACPA were; Fibβ60–74 (63%), Vim60–75 (56.6%), Fibβ36–52 (55.1%), Fil307–324 (54.9%), CEP-1 (53.7%) and Pept5 (52.0%) besides CCP2 (67.5%). Adding all ACPAs gave additional 13.1% of positivity in the anti-CCP2 negative group, yielding a positivity of 77.5%. The median (IQR) number of positive ACPA-peptide was 8 (11). There was a high degree of correlation between the antibodies, e.g., anti-Fibβ60–74 vs. -Vim60–75, -Fibβ36–52 or anti-CCP2 antibodies and also anti-Fil307–324 vs. -Fibβ36–52, -F4 R-Cit or anti-CCP2 antibodies (rs 0.692–0.79). Positivity for all antibodies was associated with higher ESR (baseline and AUC<sub>24)</sub>. A number of antibodies were associated with both high DAS28 (baseline and AUC<sub>24</sub>) and radiological findings/progression (anti-CCP2, - Fil307–324, -Vim60–75 and Vim 2–17, and -CEP1 antibodies), whilst some others were more associated with inflammation (DAS28, baseline and AUC<sub>24</sub>) (anti-Fibβ60–74, -Pept5 and -F4R-cit antibodies) and others more with radiological destruction/progression (anti-Fibβ36–52, -Fibβ74, -PeptZ1, -F4 Cit-R antibodies). Partial least squares regression analyses confirmed the results with significant correlation between radiological progression and antibodies against Vim2–17, Fibβ36–52, CEP1, Fibα621–635, and CCP2 and between DAS28AUC<sub>24</sub> and Vim60–75, Vim2–17, Fibα621–635 and F4-R-Cit. Patients treated with biologics during the first 24 months (11.2%) were significantly more frequent positive for anti-CCP2, -Vim60-75, -Fibα36–50, -PeptZ1 and -PeptZ2 antibodies vs. being negative. <h3>Conclusions</h3> Analyses at baseline, of the ACPA specificity profiles allowed different patterns of disease activity and radiological progression during the first 24 months of the disease to be identified. <h3>Disclosure of Interest</h3> None declared