Abstract
Native C-reactive protein (nCRP) is a non-specific marker of inflammation being claimed as a bystander in several chronic disorders. Accumulating evidence indicates that nCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci. This suggests that mCRP may be a superior disease marker with improved specificity and clear causality to the underlying pathogenesis. However, the lack of a feasible assay to quantify mCRP in clinical samples precludes the assessment of that suggestion. Here we report the development of a sandwich ELISA assay for quantification of plasma mCRP using commercially available reagents. Our assay is reproducible and highly conformation-specific showing a reliable detection limit of 1 ng/mL. We further show that mCRP appears to be a better marker than nCRP in several skin-related autoimmune disorders. This assay thus provides a useful tool to examine the clinical significance and utility of mCRP.
Highlights
Native C-reactive protein is a major human acute phase reactant that responds to tissue damage or infection by rapidly increasing its blood concentrations [1, 2]
Native C-reactive protein is composed of five identical subunits that are induced to dissociate at inflammatory loci [7,8,9,10,11] upon encountering damaged membranes [12,13,14,15,16,17,18,19,20,21], amyloid aggregates [22], neutrophil extracellular traps [23], or acidic pH [24]
Develop a highly specific ELISA assay to measure plasma levels of monomeric CRP (mCRP) based on commercially available reagents
Summary
Native C-reactive protein (nCRP) is a major human acute phase reactant that responds to tissue damage or infection by rapidly increasing its blood concentrations [1, 2] It has been widely used as a non-specific marker of inflammation in clinical practice. A minor increase in the circulating level of nCRP, originally considered as non-pathological, is found to be associated with the risk and prognosis of several chronic inflammatory disorders, including cancer [3] and cardiovascular disease [4] Those associations are usually moderate and are shown to be non-causal by large-scale genetic studies [5, 6]. Quantification of Plasma mCRP develop a highly specific ELISA assay to measure plasma levels of mCRP based on commercially available reagents
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