Presence of multimeric isoforms of human C-reactive protein in tissues and blood

Abstract

The baseline concentration of C-reactive protein (CRP) has been associated with a wide array of human diseases. In epidemiological studies and in the clinic, CRP is typically measured as a pentamer, composed of 5 identical CRP subunits. The present study aimed to determine whether other isoforms were present in the blood by examining CRP conformations. Transgenic rats expressing human CRP under the mouse albumin promoter were generated and genotyped. Non-reducing western blotting was performed using the blood and tissues of transgenic rats and human patients. CRP concentrations in human blood were examined by enzyme-linked immunosorbent assay. In addition to the pentameric isoform, CRP was detected as a trimer and tetramer in the blood of human CRP transgenic rats. Furthermore, trimeric and tetrameric CRP was observed in various tissues, including aorta, liver, kidney, pancreas, heart and skeletal muscle. Notably, these two isoforms appeared to be age-associated, as they were detected only in the blood and tissues of older transgenic rats. The existence of additional CRP isoforms was confirmed in the blood of human patients by non-reducing western blotting. Clinical and epidemiological studies typically focus on CRP concentration. However, the results of the present study suggest that, in addition to concentration, CRP conformation may require analysis.