The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia.
OBJECTIVE
To determine the fine specificity of anti-citrullinated protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied.


METHODS
A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA.


RESULTS
In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5-20) months. Reactivity to each peptide was significantly associated with arthritis development (p<0.001). The ACPA repertoire did not differ between patients who did or did not develop arthritis. Among aCCP-positive patients, patients recognising two or more additional citrullinated peptides developed arthritis more often (p=0.04). The number of recognised peptides was positively associated with the aCCP level (p<0.001). Crossreactivity between different peptides was minimal.


CONCLUSIONS
Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
Department of Immunopathology, Sanquin Research and Landsteiner Laboratorium, Academic Medical Center, Amsterdam, The Netherlands. l.vandestadt@sanquin.nl
Lotte A
LA
van de Stadt
Ann R
AR
van der Horst
Margret H M T
MH
de Koning
Wouter H
WH
Bos
Gerrit Jan
GJ
Wolbink
Rob J
RJ
van de Stadt
Ger J M
GJ
Pruijn
Ben A C
BA
Dijkmans
Dirkjan
D
van Schaardenburg
Dörte
D
Hamann
D000328:Adult; D018771:Arthralgia / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006650:Histocompatibility Testing; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D012217:Rheumatoid Factor / Q000097:blood
D001323:Autoantibodies; D015415:Biomarkers; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor