Background/Purpose:

The HLA-DRB1 shared epitope (SE) and antibodies to cyclic citrullinated peptides (anti-CCP) are important to the susceptibility to rheumatoid arthritis (RA), and are thought to be involved in pathogenesis. Clinically, their presence identifies patients with more severe disease. Few studies have examined their combined effect on RA outcome. We studied a large cohort of RA patients focusing on the association of radiographic joint damage with the presence of the SE and anti-CCP. 

Methods:

A radiograph of both hands and wrists was used to measure erosions and joint-space narrowing in patients with RA, using the technique developed by Sharp et al. The SE was genotyped using sequence-specific primer amplification, and anti-CCP was measured using ELISA. An anti-CCP concentration of 20 IU or higher was considered positive. Patients were followed over time with repeated hand radiographs.  We used generalized estimating equations (GEE) with the Sharp score as a dependent variable to examine association between the SE and anti-CCP.  

Results:

We studied 1,328 RA patients. Of these, 1,264 (95%) had hand radiographs, as well as SE and anti-CCP results.  There were 3,824 radiographs, or 3.0 films per patient, over 8,700 patient-years of observation (6.9 years per patient).   The Sharp score at baseline was 47 (SD 61, range 0 to 294). The Sharp score progressed at a rate of 4.09 units per year (95% CI 3.96, 4.22) in the cohort considered as a whole.  Among the 157 patients who were negative for both the SE and anti-CCP, the Sharp score progressed at a rate of 2.76 units per year (2.44, 3.08). Among 449 patients who were positive for either the SE or the anti-CCP, the Sharp progression rate was 4.02 (3.82, 4.22, P < 0.001). Among 658 patients who were positive for both the SE and anti-CCP, Sharp progression rate was 4.50 (4.34, 4.67, P < 0.001).   We also examined at what point in time the mean Sharp score diverged significantly between the groups defined by SE and anti-CCP. Compared to patients who had negative SE and negative anti-CCP, patients who had positive SE and/or positive anti-CCP did not develop significantly higher Sharp score until 17 years of disease duration had passed. 

Conclusion:

Joint damage progressed more rapidly among RA patients who had positive SE and/or anti-CCP. However, it was not until well into the second decade of disease that the amount of damage in the patients with positive SE and/or positive anti-CCP became significantly different from those in whom these markers were negative.

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« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/joint-damage-progression-in-rheumatoid-arthritis-role-of-the-hla-drb1-shared-epitope-and-anti-ccp/