Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

The Development of the ACPA Repertoire Prior to the Onset of Clinical RA.

van de Stadt4,  Lotte A., de Koning2,  Margret, van de Stadt1,  Rob J., Wolbink2,  Gertjan, Dijkmans5,  B. A. C., Hamann3,  Dörte, van Schaardenburg2,  Dirkjan

Jan van Breemen Institiute
Jan van Breemen Institute
Sanquin Diagnostics
Sanquin Research
VU Medical Centre, Amsterdam, The Netherlands


Rheumatoid Arthritis is an auto-immune disease in which anti-citrullinated protein antibodies (ACPA) probably play a pathogenic role. The ACPA response is already expanded before the first symptoms of RA and remains stable thereafter [1].


To explore the degree of epitope spreading prior to onset of clinical RA and the pattern of auto-antigen reactivity at the start of the immune response.


Multiple serial serum samples of 79 RA patients who donated blood before disease onset were available for analysis. 47 patients tested aCCP2 positive prior to onset of clinical RA. Of these patients a median of 5 (IQR 3–7) sequential pre-RA sera spaced one to two years apart were tested for reactivity to 5 distinct citrullinated peptides in an ELISA. Two fibrinogen, 1 vimentin, 1 alpha-enolase and 1 cyclic citrullinated peptide (CCP1) were tested. Reactivity to the 5 corresponding arginine peptides was also tested.


Four anti-CCP2 positive patients (9%) did not show reactivity to any peptide. In the selected patient samples seroconversion to ACPA was detected in 24 patients (51%). In 14 of these patients (58%) the immune response started with reactivity to one peptide. In four patients (17%) it started with two peptides, in four (17%) it started with three peptides and in two (8%) it started with four peptides. The number of recognised peptides increased over time (figure 1). Median antibody titers directed to all peptides also increased over time. The ACPA response did not start with reactivity to one particular peptide (figure 2).


ACPA epitope spreading occurs over several years prior to onset of clinical RA. None of the tested auto-antigens is solely responsible for the initial auto-immune response.

1.van der Woude, D.,, Ann Rheum Dis, 2010, doi:10.1136/ard.2009.124537.

To cite this abstract, please use the following information:
van de Stadt, Lotte A., de Koning, Margret, van de Stadt, Rob J., Wolbink, Gertjan, Dijkmans, B. A. C., Hamann, Dörte, et al; The Development of the ACPA Repertoire Prior to the Onset of Clinical RA. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1091
DOI: 10.1002/art.28858

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