Anti-CCP antibodies are a useful diagnostic tool, particularly among seronegative rheumatoid arthritis (RA) patients. The presence of anti-CCP antibodies confers prognostic utility for radiographic and functional outcomes, according to a new study published in the journal Rheumatology.¹ These results may allow for more effective management of early RA.

The new study evaluated the second-generation anti-CCP test in 182 patients with RA and 121 control patients with connective tissue disease. All RA patients reported fewer than 24 months of symptoms. Measurements for C-reactive protein, rheumatoid factor (RF), HLA typing (SE), and anti-CCP2 antibodies were taken at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and x-rays were performed at 0, 12, and 24 months.

The anti-CCP antibody test demonstrated a specificity of 91% and a sensitivity of 81% for RA when compared with control patients. In RF-negative patients, specificity measured 92% and sensitivity, 60%. Reasearchers used the Larsen method to determine the predictor of change in joint destruction from 0 to 24 months. In patients with RA the predictor of change was the presence of the shared epitope (P <.05); in patients without RA, the predictor of change was an anti-CCP antibody titer >100 (P <.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup, an anti-CCP antibody titer >100 predicted a poor functional response at 24 months (P <.05).

"Such findings are of practical [importance] for clinical decision making in early disease," conclude the researchers, led by Mark Quinn, MD, a rheumatologist at Chapel Allerton Hospital in Leeds, United Kingdom. "Prognostic assessment at the time of first presentation is crucial, particularly given the new early aggressive therapeutic approaches and the availability of expensive biological agents. In this cohort, using [anti-CCP] antibodies would appear to select seronegative RA patients with poor prognosis and so it may have important implications for patient management."

Growing role for anti-CCP testing in RA

"Anti-CCP antibodies are a useful adjunct serological marker for RA when used with other markers, such as rheumatoid factor," says Kristine Kuhn, PhD, a research assistant in the department of rheumatology at the University of Colorado in Denver. "It seems highly specific for RA, ranging from 96% to 100%," she tells CIAOMed.

"Anti-CCP is ... important ... clinically, particularly when you question a diagnosis and want additional information to help you make that diagnosis," explains Dr. Kuhn. "As far as how it will be used to determine therapies, studies are now looking at arrays of biomarkers to detect subsets of RA and [determine] whether those [subpopulations] as defined by biomarkers are responsive to different therapies."

Kuhn and her colleagues recently published a study designed to further evaluate the role of anti-CCP antibodies; using a mouse model of collagen-induced arthritis, the study demonstrated that anti-CCP antibodies are also involved in the pathogenesis of RA.² The study suggests that targeting anti-CCP antibodies may prove to be a useful preventive strategy.

"It wasn't until my study that we knew [anti-CCP antibodies] could play a role in pathogenesis of the disease," Dr. Kuhn tells CIAOMed. "They actually participate in the disease process by binding antigen within the joints and further propagating the immune response that leads to erosive disease."

References

1. Quinn MA, Gough AKS, Green MJ, et al. Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology. 2005;45:478-480.
2. Kuhn KA, Kulik L, Tomooka B, et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest. 2006;116:961-973.