Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Abstract

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course.

Figure 1

Swelling of the MCP and PIP joints at inclusion and follow-up. Joint swelling (mean and 95% confidence interval [CI]) of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands at inclusion and at 2 and 4 years follow-up in rheumatoid arthritis patients with (CCP+) and without (CCP-) anti-cyclic-citrullinated peptide antibodies. L, left; R, right.

Figure 2

Radiological destruction in patients with and without anti-cyclic-citrullinated peptide antibodies.Total Sharp–van der Heijde scores (mean ± standard error of the mean) at inclusion and at 2 and 4 years follow-up in rheumatoid arthritis patients with (CCP+) and without (CCP-) anti-cyclic-citrullinated peptide antibodies.

Figure 3

Erosion and joint space narrowing scores of MCP and PIP joints at Inclusion and follow-up. Erosion and joint space narrowing scores of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands (means and 95% confidence interval [CI]) at inclusion and at 2 and 4 years follow-up in rheumatoid arthritis patients with anti-cyclic-citrullinated peptide antibodies. L, left; R, right.