Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response.
OBJECTIVE
The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration.


METHODS
IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later.


RESULTS
IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years.


CONCLUSIONS
These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.
Verpoort
K N
KN
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. K.N.Verpoort@lumc.nl
Jol-van der Zijde
C M
CM
Papendrecht-van der Voort
E A M
EA
Ioan-Facsinay
A
A
Drijfhout
J W
JW
van Tol
M J D
MJ
Breedveld
F C
FC
Huizinga
T W J
TW
Toes
R E M
RE
D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology*; D013997:Time Factors
D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide