Citation, DOI, disclosures and article data
At the time the article was created Hamish Smith had no recorded disclosures.View Hamish Smith's current disclosures
C-reactive protein (CRP) is an acute phase reactant commonly measured in clinical practice as a marker of inflammation and to monitor disease severity, disease course and treatment response. It should not be confused with protein C (an anticoagulant) or C-peptide (a component of proinsulin).
Cellular injury, infection or neoplasia results in the up-regulation and expression of various cytokines and chemical mediators. Interleukin-6 causes the downstream transcription and production of C-reactive protein in hepatocytes 1.
CRP is important in binding to damaged or injured cellular components (e.g. damaged cell membranes) and pathogen components (e.g. bacterial cell wall proteins) and potently activates the classical complement pathway through binding C1q 2,3.
Synthesis of C-reactive protein commences soon after a stimulus and levels can reach above 5 mg/L in 6 hours and usually peak around the 48 hour mark. The half-life of C-reactive protein is 19 hours and this rate is constant in both diseased and healthy states. The total level of C-reactive protein is therefore determined by the strength and continued presence of the stimulating infection or injury 4. This makes levels useful to track disease.
The normal plasma level of CRP is between 0.8 and 3.0 mg/L 4. CRP levels in asymptomatic patients increase with age, possibly due to the increased prevalence of undiagnosed pathology (e.g. cancer) 5. CRP levels are relatively stable between individuals and from day to day in the absence of disease 4,5. CRP can become drastically elevated by a factor of one hundred to one thousand to over 500 mg/L 1.
CRP is very sensitive for detecting inflammation, cellular injury, neoplasia and infection, it however is non-specific and numerous conditions elevate it. A short (and non-exhaustive) list is provided below 1.
- infection: bacterial (e.g. pneumonia), viral (e.g. viral respiratory tract infection), mycobacterial (e.g. tuberculosis), fungal (e.g. pulmonary candidiasis)
- autoimmune disease: Crohn disease, rheumatoid arthritis, juvenile idiopathic arthritis, vasculitis, autoimmune hepatitis
- cellular injury: myocardial infarction, acute pancreatitis
- trauma: burns, post-surgery
- malignancy: lymphoma, solid organ tumors (e.g. colon adenocarcinoma)
Absent or minor elevation
The following conditions do not usually result in substantially elevated C-reactive protein levels: scleroderma, SLE, dermatomyositis, ulcerative colitis, and leukemia. This fact may be useful in distinguishing between certain diseases 1.
Studies have shown that healthy pregnant females have slightly higher CRP levels than healthy non-pregnant women. However it is not normal to be markedly elevated, in which case it should be treated in the same way as in a non-pregnant patient, and assumed to be bacterial infection in the first instance 7,8.
History and etymology
C-reactive protein was named due to its ability to precipitate the C-polysaccharide present in Streptococcus pneumonia 1.
- 1. Mark B. Pepys, Gideon M. Hirschfield. C-reactive protein: a critical update. (2003) The Journal of Clinical Investigation. 111 (12): 1805. doi:10.1172/JCI18921 - Pubmed
- 2. Pepys MB, Rowe IF, Baltz ML. C-reactive protein: binding to lipids and lipoproteins. (1985) International review of experimental pathology. 27: 83-111. Pubmed
- 3. Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. (1999) Structure (London, England : 1993). 7 (2): 169-77. doi:10.1016/S0969-2126(99)80023-9 - Pubmed
- 4. Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. (1993) The Journal of clinical investigation. 91 (4): 1351-7. doi:10.1172/JCI116336 - Pubmed
- 5. Hutchinson WL, Koenig W, Fröhlich M, Sund M, Lowe GD, Pepys MB. Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. (2000) Clinical chemistry. 46 (7): 934-8. Pubmed
- 6. Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. (1983) Advances in immunology. 34: 141-212. Pubmed
- 7. Wirestam L, Pihl S, Saleh M, Wetterö J, Sjöwall C. Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy. Front Immunol. 2021;12:722118. doi:10.3389/fimmu.2021.722118 - Pubmed
- 8. Kristensen K, Wide-Swensson D, Lindström V, Schmidt C, Grubb A, Strevens H. Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia. Gynecol Obstet Invest. 2009;67(4):275-80. doi:10.1159/000214081 - Pubmed