Background/Purpose:  Antibodies against cyclic citrullinated peptides (anti-CCP) have been suggested to identify a more severe phenotype of rheumatoid arthritis. In this study we have analysed a number of antibodies against citrullinated peptides (ACPA) using a multiplex platform in an inception cohort of early RA in relation to disease inflammation and progressive severity.

Methods:  Patients with early RA (≤12 months of symptoms) fulfilling the 1987 ARA criteria (n=1012, 681f/331m, mean age56.9±14.0 years) were sampled at the time of diagnosis and evaluated using disease activity score 28 (DAS28) (at baseline, 6, 12, 18 and 24 months) and with radiography using Larsen score (baseline and 24 months). Baseline plasma samples were analysed for presence of 17 different antibodies; ACPA (Fibrinogen α36-50 (Fibα36-50), 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)), or mutated proteins (Bla26, Pept1, Pept5, PeptZ1, PeptZ2) analysed using a custom-made microarray assay based on the ImmunoCAP ISAC system (Phadia AB, Sweden). Cut-off levels set at the 98th percentile of controls. Anti-CCP2 was analysed using ELISA (Euro Diagnostica, Sweden) and rheumatoid factor (RF) according to routine methods with cut-off at 95%.

Results:

The most frequent positive 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%) and RF (74.3%). The median (IQR) number of ACPA positivity was 8 (11). Adding all ACPAs gave additional 13.1% of positivity in the anti-CCP2 negative group, yielding a total positivity of 77.5%. Positivity for CCP-1, Vim60-75, Fibα36-50, Pept5 and Vim2-17 was associated with area under curve (AUC) DAS28 during the 24 months compared with negativity (p<0.05). Increased ESR at baseline was associated with positivity vs. negativity for all antibodies except Fibβ62-78(72), Fibβ62-78 (74) and Pept1 (p<0.05). Positivity for Fil307-324, CEP-1, Fibα36-50, Fibα621-635, Fibβ36-52, Vim60-75, Vim2-17, PeptZ1 and Pept1 were significantly associated with radiological progression (p<0.05). CEP-1, Fibα621-635, Fibα36-50 and PeptZ2 remained significant in a logistic stepwise regression analysis adjusted for sex. Overall 69.1% were good-moderate EULAR responders, no significant relationships between antibodies and response to treatments were found except for positivity for Fibβ36-52 adjusted for all analysed antibodies, sex and being a smoker (p=0.008). Of the patients treated with biologics during the first 24 months (11.2%), positivity for antibodies against CCP2, Vim60‑75, Fibα36-50, PeptZ1 and PeptZ2 were significantly more frequent vs. negativity.

Conclusion:

Disease activity and radiological progression are associated with different ACPA reactivities at the time of diagnose and during the 24 months follow up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/do-specific-anti-citrullinated-antibodies-predict-different-phenotype-of-rheumatoid-arthritis/