We previously reported that approximately half of the patients with rheumatoid arthritis (RA) have specific serologic abnormalities (elevated serum concentrations of IgM rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) starting several years before the onset of symptoms. In this study, the presence of serologic signs of inflammation in patients with preclinical RA was investigated with serial measurements of C-reactive protein (CRP).
Seventy-nine patients (61% female; mean age at onset of symptoms 51 years) who had been blood donors before the onset of RA were identified. Frozen serum samples from each donor were retrieved, together with 1 sample from a control donor matched for age, sex, and date of donation. CRP was measured using a highly sensitive latex-enhanced assay. The dates of donation were categorized into 15 1-year periods preceding the onset of RA symptoms. For each period, the median CRP levels in the patient and control groups were compared using the Mann-Whitney U test. The course of CRP concentrations over time in the patient group was estimated with random coefficient analysis.
A median of 13 samples (range 1-51) per patient were available; the earliest donation was made a median of 7.5 years (range 0.4-14.5 years) before the onset of symptoms. A total of 1,078 patient samples and 1,071 control samples were tested. For all 1-year periods, the median CRP concentration was increased in the patient group compared with the control group, but this difference was statistically significant only for the periods 0-1 year, 1-2 years, and 4-5 years before the onset of symptoms. The CRP concentration increased significantly over time in patients with preclinical RA; levels were slightly higher in the group of patients who had serologic abnormalities before the onset of symptoms than in those without such serologic abnormalities.
After observing specific serologic abnormalities 5 years before the onset of RA symptoms, we now report increased levels of CRP in blood donors in whom RA later developed; these increases were most common within the 2 years before the onset of symptoms. The preclinical increase in CRP levels was observed both in donors with and in those without serologic abnormalities.