RESEARCH - Epitope spreading of the anti-CCP antibody response occurs before disease onset and is associated with disease course of early arthritis

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Ann Rheum Dis 2010;69:1554-1561 doi:10.1136/ard.2009.124537

Basic and translational research

Extended report

Epitope spreading of the anti-citrullinated protein antibody response

occurs before disease onset and is associated with the disease course

of early arthritis

Diane van der Woude1, Solbritt Rantapää-Dahlqvist2, Andreea

Ioan-Facsinay1, Carla Onnekink3, Carla M Schwarte3, Kirsten N

Verpoort1, Jan W Drijfhout4, Tom W J Huizinga1, Rene E M Toes1, Ger J

M Pruijn3

+ Author Affiliations

1Department of Rheumatology, Leiden University Medical Centre, Leiden,

The Netherlands

2Department of Rheumatology, Umeå University Hospital, Umeå, Sweden

3Department of Biomolecular Chemistry, Radboud University Nijmegen,

Nijmegen, The Netherlands

4Department of Immunohaematology and Blood Transfusion, Leiden

University Medical Centre, Leiden, The Netherlands

Abstract

Background Anti-citrullinated protein antibodies (ACPA) are the most

predictive factor for the development of rheumatoid arthritis (RA).

Objective To investigate whether the recognition of citrullinated

epitopes changes during disease onset or progression, by studying the

fine specificity of ACPA in serum samples collected throughout the

disease course, from before the onset of arthritis to longstanding RA.

Methods Antibodies recognising five distinct citrullinated antigens

were determined by enzyme-linked immunosorbent assay. Serum samples

from 36 individuals who had donated blood before and after disease

manifestation were used to investigate the development of

citrullinated antigen recognition before disease onset. The

association of ACPA reactivities with disease outcome was studied

using sera from anti-cyclic citrullinated peptide-2 (CCP2)-positive

patients with undifferentiated arthritis (UA) who did or did not

progress to RA (UA–RA n=81, or UA–UA n=35). To investigate the ACPA

recognition profile in patients with RA over a prolonged period of

time, baseline serum samples from 68 patients were compared with

samples obtained 7 years later.

Results The number of recognised citrullinated peptides increased in

the period preceding disease onset. At the time of disease

manifestation, patients with UA who later developed RA recognised

significantly more peptides than UA–UA patients. At later stages of

the disease course, the ACPA fine specificity did not change.

Conclusion Epitope spreading with an increase in the recognition of

citrullinated antigens occurs before the onset of RA. Immunological

differences in ACPA fine specificity between UA–UA patients and UA–RA

patients are present at baseline and are associated with the future

disease course.

http://ard.bmj.com/content/69/8/1554.abstract?etoc

Not an MD