Minimal Inflammation, Acute Phase Response and Avoidance of Misclassification of Vitamin A and Iron Status in Infants – Importance of a High-Sensitivity C-Reactive Protein (CRP) Assay

The acute phase response is known to affect many biological parameters used to assess the iron and vitamin A status. Usually, C-reactive protein (CRP) values higher than 5 to 10 mg/L are taken as indicative of this response. Here we report changes occurring at much lower CRP values. A range of parameters (clinical chemistry, retinol, vitamin E, carotenoids, thyroid status, blood count, immunology) were measured in 101 healthy one-year-old children with no or only minimal symptoms of airway infection and CRP values below 6 mg/L on routine testing. Additionally, CRP values were measured by a high-sensitivity assay (detection limit 0.2 mg/L). When determined by a more sensitive assay, CRP values (median, 0.26 mg/L) revealed highly significant associations with parameters known to be influenced by the acute phase response. Using a limit of 0.6 mg/L (75th percentile), significantly lower levels were observed for transthyretin, iron, retinol, and beta-carotene in the group with the higher CRP levels. This relationship was confirmed intra-individually in a subgroup of 21 children who underwent a second blood draw about four weeks after the first one. The acute phase response is triggered at very low inflammatory levels with CRP values considerably lower than 5 to 10 mg/L, and can occur in apparently healthy children. A high-sensitivity CRP assay is necessary to detect this low level, and in the case of iron or vitamin A, it can help to avoid misclassification of the nutritional status.