Implications of Human C‐Reactive Protein Recognition by Specific and Non‐specific Antibodies

Abstract

C-reactive protein (CRP) has been associated with increased risk of cardiovascular disease and its complications. Although native CRP exists mainly in a pentameric configuration, the monomeric form is postulated to possess distinctive biological properties including promotion of vascular proinflammatory phenotype. Here we compared immunological reactivities of the pentameric and monomeric CRP. We used the Western blotting technique to test the interactions between monomeric CRP and a number of immunoglobulins from different species. The monomeric form was prepared by heat denaturation under reducing conditions followed by SDS-polyacrylamide gel electrophoresis. The monomeric protein was transferred to nitrocellulose and probed with immunoglobulins as appropriate. Two other proteins of the pentraxin family, serum amyloid P component (SAP) and the long pentraxin (PTX3), were tested in the same manner. CRP in its denatured monomeric form, but not in its native pentameric conformation, associates promiscuously with IgG molecules, including normal human IgG. This association is intrinsic to CRP and is not observed with any other protein we examined. Monomeric CRP is uniquely reactive with immunoglobulins regardless of source or specificity. In contrast, other pentraxins require specific antibodies for recognition and detection. These findings may have therapeutic implications as being relevant to development and progression of atherosclerotic disease.