Study of serum calprotectin level in rheumatoid arthritis: unexpected low level and possible explanations

Assessment of disease activity in rheumatoid arthritis (RA) is crucial to optimize the response to treatment and prevent radiographic progression. DAS28 is the most commonly used disease activity index, which incorporates either erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Several studies showed that using ESR and/or CRP in assessing disease activity falls short of detecting a significant portion of patients with active disease. Calprotectin (CLP) is an interesting protein that was found to be a promising biomarker of disease activity in RA patients’ sera when CRP is normal. This study aimed to measure serum CLP level in 50 RA patients with different grades of disease activity and compare its level with age- and sex-matched control.

In this case–control study, the mean serum CLP level was significantly lower in RA patients (25.94 ± 25.87 ng/ml) compared to the control group values (53.02 ± 77.93 ng/ml), p < 0.001. The measured serum CLP in RA patients was lower than its level in other published studies. No significant difference was found between patients with different disease activity grades in the serum CLP level (H = 4.28, p = 0.23). Serum samples were collected and stored from RA patients over 4 months and from the control subjects over 1.5 months and were stored at –80 °C until analysis was performed according to the manufacturer’s instruction.

The low level of serum CLP among RA patients is most probably due to proteolysis related to storage conditions. Pre-analytic factors like the type of blood sample, whether the sample is fresh or frozen, and duration of storage exert an effect on serum CLP level when measured by enzyme-linked immunosorbent assay.