Presence of multimeric isoforms of human C-reactive protein in tissues and blood
1Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Insights
C-reactive protein (CRP) exists beyond its usual pentamer form. Researchers found trimeric and tetrameric CRP in blood and tissues, suggesting conformation analysis is crucial for disease studies.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- C-reactive protein (CRP) concentration is a known disease biomarker.
- CRP is typically measured as a pentameric isoform in clinical settings.
- The presence of other CRP isoforms and their significance remain largely unexplored.
Purpose of the Study:
- To investigate the existence of different C-reactive protein (CRP) isoforms in blood.
- To examine CRP conformations beyond the standard pentameric form.
- To determine if these isoforms are associated with age and present in various tissues.
Main Methods:
- Generation and genotyping of transgenic rats expressing human CRP.
- Non-reducing western blotting on blood and tissues from transgenic rats and human patients.
- Enzyme-linked immunosorbent assay (ELISA) for CRP concentration in human blood.
Main Results:
- Detection of trimeric and tetrameric CRP isoforms in addition to the pentameric form in transgenic rat blood.
- Trimeric and tetrameric CRP were found in various tissues of older transgenic rats.
- Confirmation of additional CRP isoforms in human blood samples using non-reducing western blotting.
Conclusions:
- C-reactive protein (CRP) exists in multiple isoforms, including trimers and tetramers, in addition to the commonly measured pentamer.
- These alternative CRP isoforms appear to be age-associated and present in diverse tissues.
- CRP conformation analysis, alongside concentration, may be necessary for accurate clinical and epidemiological disease assessment.
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.
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