RT Journal Article
SR Electronic
T1 Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1554
OP 1561
DO 10.1136/ard.2009.124537
VO 69
IS 8
A1 Diane van der Woude
A1 Solbritt Rantapää-Dahlqvist
A1 Andreea Ioan-Facsinay
A1 Carla Onnekink
A1 Carla M Schwarte
A1 Kirsten N Verpoort
A1 Jan W Drijfhout
A1 Tom W J Huizinga
A1 Rene E M Toes
A1 Ger J M Pruijn
YR 2010
UL http://ard.bmj.com/content/69/8/1554.abstract
AB 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.