Background Anti-citrullinated protein/peptide antibodies (ACPA) have been suggested to identify a more severe phenotype of rheumatoid arthritis (RA).
Objectives 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
Methods 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 at 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).
Results 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 AUC24). A number of antibodies were associated with both high DAS28 (baseline and AUC24) 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 AUC24) (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 DAS28AUC24 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.
Conclusions 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.
Disclosure of Interest None declared
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