Rheumatoid arthritis and early indicators of disease

A chronic autoimmune disease marked by severe inflammation and joint, rheumatoid arthritis (RA) is a major cause of pain and disability.

Since treatment improves outcome when administered soon after disease onset, the availability of predictive tests would allow earlier identification of patients and institution of more effective therapy. In addition, such markers could allow new approaches to prevention.

Can blood test predict disease in patients who develop rheumatoid arthritis? For insights, a team of researchers from the Netherlands, led by Ben A.C. Dijkmans and supported by the Dutch Arthritis Foundation, set out to investigate the evidence in the bloodstream of RA patients, beginning with samples donated 15 years before the onset of disease symptoms. Published in the August 2004 issue of Arthritis & Rheumatism, their findings shed new light on the presence of inflammation in the preclinical phase of RA, in patients both with and without autoantibodies, abnormal proteins in the blood associated with autoimmune disease.

Collecting samples from an established blood bank in Amsterdam, Dijkmans and his team focused on 79 RA patients – 61 percent women, with a mean age of 51 years at the time of diagnosis. For each RA sample, they obtained a control sample donated by a healthy patient, matched for sex, age and time of blood donation. Among the samples from RA patients, the researchers found signs of early inflammation, measured by elevated levels of C-reactive protein (CRP) in the bloodstream. RA patients had consistently higher levels of CRP than the healthy controls throughout the 15 years preceding outward disease symptoms. The concentration of CRP, however, was most pronounced, and significant, within the two years before a confirmed diagnosis of RA. CRP has also been used a marker to identify people at risk for coronary artery disease.

Interestingly, elevated levels of CRP were identified in all of the RA patients – including those with no signs of destructive autoantibodies, about half of the total samples studied.

"Patients who had serologic abnormalities before the onset of symptoms had slightly higher CRP concentrations compared with patients without serologic abnormalities," notes Dijkmans. "However, both groups showed a very similar pattern of increase in the CRP concentration over time, which does not indicate a pivotal role for autoantibodies in the development of inflammation during the preclinical phase of RA. Rather, the somewhat higher CRP concentration observed in patients with serologic abnormalities suggest that the production of autoantibodies is a phenomenon secondary to an increased level of inflammation in these patients."

The differences in CRP concentration may well have clinical implications for RA, as a factor predictive of later symptomatic inflammation. Yet, as Dijkmans stresses, this study's findings should not influence decision-making in individual patient care. More research is needed.

The articles – as well as free abstracts – are available online via Wiley InterScience at http://www.interscience.wiley.com/journal/arthritis.