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Copyright (c) 2025 Salman Saad Thamer Alanazi, Sultan Hadi Alanazi, Tariq Mukhaymir Hamdan Alharbi, Alawyah Abker Ahmed Ageel, Mariam swilam daghash alqahtani
This work is licensed under a Creative Commons Attribution 4.0 International License.
C-Reactive Protein: Clinical Relevance and Interpretation From Medical Laboratory and Health Informatics Perspectives
Corresponding Author(s) : Salman Saad Thamer Alanazi
Saudi Journal of Medicine and Public Health,
Vol. 2 No. 2 (2025)
Abstract
Background: C-reactive protein (CRP) is a highly conserved acute-phase biomarker synthesized by hepatocytes in response to inflammatory stimuli, primarily mediated by IL-6. It exists in pentameric (pCRP) and monomeric (mCRP) isoforms, each with distinct immunological functions. CRP plays an essential role in innate immunity through ligand binding, complement activation, and phagocytic enhancement.
Aim: To provide a comprehensive review of the clinical relevance, diagnostic applications, and factors affecting CRP measurement from medical laboratory and health informatics perspectives.
Methods: This narrative review synthesizes experimental, clinical, and epidemiological findings regarding CRP structure, regulation, clinical utility, diagnostic techniques, and interfering variables. It also incorporates FDA-cleared assay technologies and point-of-care innovations.
Results: CRP demonstrates rapid kinetic response, rising within hours of inflammation and declining promptly upon resolution. Its elevations correlate with infectious, autoimmune, traumatic, and neoplastic conditions. High-sensitivity CRP (hsCRP) enables cardiovascular risk stratification by detecting low-grade inflammation. Elevated CRP levels also predict venous thromboembolism risk, cancer propensity, heart failure progression, and frailty in aging populations. Numerous factors—including medications, lifestyle, genetics, and comorbidities—modulate CRP concentrations and complicate interpretation.
Conclusion: CRP remains a vital biomarker for diagnosing and monitoring inflammation across diverse clinical scenarios. Its usefulness depends on proper contextual interpretation, integration with clinical findings, and awareness of interfering variables. Advances in diagnostic technology have improved CRP measurement accuracy, accessibility, and clinical value.
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- Zhou HH, Tang YL, Xu TH, Cheng B. C-reactive protein: structure, function, regulation, and role in clinical diseases. Front Immunol. 2024;15:1425168.
- Melnikov I, Kozlov S, Saburova O, Avtaeva Y, Guria K, Gabbasov Z. Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives. Int J Mol Sci. 2023 Jan 20;24(3)
- Rajab IM, Hart PC, Potempa LA. How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression. Front Immunol. 2020;11:2126.
- Cleland DA, Eranki AP. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Apr 23, 2023. Procalcitonin.
- Jungen MJ, Ter Meulen BC, van Osch T, Weinstein HC, Ostelo RWJG. Inflammatory biomarkers in patients with sciatica: a systematic review. BMC Musculoskelet Disord. 2019 Apr 09;20(1):156.
- Kramer NE, Cosgrove VE, Dunlap K, Subramaniapillai M, McIntyre RS, Suppes T. A clinical model for identifying an inflammatory phenotype in mood disorders. J Psychiatr Res. 2019 Jun;113:148-158.
- Vanderschueren S, Deeren D, Knockaert DC, Bobbaers H, Bossuyt X, Peetermans W. Extremely elevated C-reactive protein. Eur J Intern Med. 2006 Oct;17(6):430-3.
- You Y. Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis. J Sports Sci. 2024 Mar;42(6):527-536.
- Dong M, Wu J, Ma Z, Peretz-Soroka H, Zhang M, Komenda P, Tangri N, Liu Y, Rigatto C, Lin F. Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip). Sensors (Basel). 2017 Mar 26;17(4)
- Eschborn S, Weitkamp JH. Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis. J Perinatol. 2019 Jul;39(7):893-903.
- Darooghegi Mofrad M, Milajerdi A, Koohdani F, Surkan PJ, Azadbakht L. Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis Factor, and Interleukin-6 in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Nutr. 2019 Apr 01;149(4):605-618.
- Dick AG, Magill N, White TCH, Kokkinakis M, Norman-Taylor F. C-reactive protein: what to expect after bony hip surgery for nonambulatory children and adolescents with cerebral palsy. J Pediatr Orthop B. 2019 Jul;28(4):309-313.
- Dix C, Zeller J, Stevens H, Eisenhardt SU, Shing KSCT, Nero TL, Morton CJ, Parker MW, Peter K, McFadyen JD. C-reactive protein, immunothrombosis and venous thromboembolism. Front Immunol. 2022;13:1002652.
- Zhang P, Mo D, Lin F, Dai H. Relationship between novel inflammatory markers derived from high-sensitivity C-reactive protein and heart failure: a cross-sectional study. BMC Cardiovasc Disord. 2025 Feb 18;25(1):111.
- Zhu M, Ma Z, Zhang X, Hang D, Yin R, Feng J, Xu L, Shen H. C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis. BMC Med. 2022 Sep 19;20(1):301.
- Burger PM, Koudstaal S, Mosterd A, Fiolet ATL, Teraa M, van der Meer MG, Cramer MJ, Visseren FLJ, Ridker PM, Dorresteijn JAN., UCC-SMART study group. C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease. J Am Coll Cardiol. 2023 Aug 01;82(5):414-426.
- Luo YF, Cheng ZJ, Wang YF, Jiang XY, Lei SF, Deng FY, Ren WY, Wu LF. Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis. BMC Geriatr. 2024 Mar 04;24(1):222.
- Lee Y, McKechnie T, Doumouras AG, Handler C, Eskicioglu C, Gmora S, Anvari M, Hong D. Diagnostic Value of C-Reactive Protein Levels in Postoperative Infectious Complications After Bariatric Surgery: a Systematic Review and Meta-Analysis. Obes Surg. 2019 Jul;29(7):2022-2029.
- Johns I, Moschonas KE, Medina J, Ossei-Gerning N, Kassianos G, Halcox JP. Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study. Open Heart. 2018;5(2):e000849.
- Berman M, Ben-Ami R, Berliner S, Anouk M, Kaufman I, Broyde A, Borok S, Elkayam O. The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature. Life (Basel). 2021 Mar 20;11(3)
- Amezcua-Castillo E, González-Pacheco H, Sáenz-San Martín A, Méndez-Ocampo P, Gutierrez-Moctezuma I, Massó F, Sierra-Lara D, Springall R, Rodríguez E, Arias-Mendoza A, Amezcua-Guerra LM. C-Reactive Protein: The Quintessential Marker of Systemic Inflammation in Coronary Artery Disease-Advancing toward Precision Medicine. Biomedicines. 2023 Sep 02;11(9)
- Guo L, Huang Y, He J, Li D, Li W, Xiao H, Xu X, Zhang Y, Wang R. Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014. Sci Rep. 2024 Jun 11;14(1):13444.
- Lopez-Roblero A, Serrano-Guzmán E, Guerrero-Báez RS, Delgado-Enciso I, Gómez-Manzo S, Aguilar-Fuentes J, Ovando-Garay V, Hernández-Ochoa B, Quezada-Cruz IC, Lopez-Lopez N, Canseco-Ávila LM. Single-nucleotide polymorphisms in the promoter of the gene encoding for C-reactive protein associated with acute coronary syndrome. Biomed Rep. 2024 Nov;21(5):150.
- Figueroa-Hall LK, Xu B, Kuplicki R, Ford BN, Burrows K, Teague TK, Sen S, Yeh HW, Irwin MR, Savitz J, Paulus MP. Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors. Transl Psychiatry. 2022 Jul 12;12(1):279.
- Bhardwaj N, Ahmed MZ, Sharma S, Nayak A, Anvikar AR, Pande V. C-reactive protein as a prognostic marker of Plasmodiumfalciparum malaria severity. J Vector Borne Dis. 2019 Apr-Jun;56(2):122-126.
- Vuong NL, Le Duyen HT, Lam PK, Tam DTH, Vinh Chau NV, Van Kinh N, Chanpheaktra N, Lum LCS, Pleités E, Jones NK, Simmons CP, Rosenberger K, Jaenisch T, Halleux C, Olliaro PL, Wills B, Yacoub S. C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study. BMC Med. 2020 Feb 17;18(1):35.
- de Souza Pires-Neto O, da Silva Graça Amoras E, Queiroz MAF, Demachki S, da Silva Conde SR, Ishak R, Cayres-Vallinoto IMV, Vallinoto ACR. Hepatic TLR4, MBL and CRP gene expression levels are associated with chronic hepatitis C. Infect Genet Evol. 2020 Jun;80:104200.
References
Zhou HH, Tang YL, Xu TH, Cheng B. C-reactive protein: structure, function, regulation, and role in clinical diseases. Front Immunol. 2024;15:1425168.
Melnikov I, Kozlov S, Saburova O, Avtaeva Y, Guria K, Gabbasov Z. Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives. Int J Mol Sci. 2023 Jan 20;24(3)
Rajab IM, Hart PC, Potempa LA. How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression. Front Immunol. 2020;11:2126.
Cleland DA, Eranki AP. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Apr 23, 2023. Procalcitonin.
Jungen MJ, Ter Meulen BC, van Osch T, Weinstein HC, Ostelo RWJG. Inflammatory biomarkers in patients with sciatica: a systematic review. BMC Musculoskelet Disord. 2019 Apr 09;20(1):156.
Kramer NE, Cosgrove VE, Dunlap K, Subramaniapillai M, McIntyre RS, Suppes T. A clinical model for identifying an inflammatory phenotype in mood disorders. J Psychiatr Res. 2019 Jun;113:148-158.
Vanderschueren S, Deeren D, Knockaert DC, Bobbaers H, Bossuyt X, Peetermans W. Extremely elevated C-reactive protein. Eur J Intern Med. 2006 Oct;17(6):430-3.
You Y. Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis. J Sports Sci. 2024 Mar;42(6):527-536.
Dong M, Wu J, Ma Z, Peretz-Soroka H, Zhang M, Komenda P, Tangri N, Liu Y, Rigatto C, Lin F. Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip). Sensors (Basel). 2017 Mar 26;17(4)
Eschborn S, Weitkamp JH. Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis. J Perinatol. 2019 Jul;39(7):893-903.
Darooghegi Mofrad M, Milajerdi A, Koohdani F, Surkan PJ, Azadbakht L. Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis Factor, and Interleukin-6 in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Nutr. 2019 Apr 01;149(4):605-618.
Dick AG, Magill N, White TCH, Kokkinakis M, Norman-Taylor F. C-reactive protein: what to expect after bony hip surgery for nonambulatory children and adolescents with cerebral palsy. J Pediatr Orthop B. 2019 Jul;28(4):309-313.
Dix C, Zeller J, Stevens H, Eisenhardt SU, Shing KSCT, Nero TL, Morton CJ, Parker MW, Peter K, McFadyen JD. C-reactive protein, immunothrombosis and venous thromboembolism. Front Immunol. 2022;13:1002652.
Zhang P, Mo D, Lin F, Dai H. Relationship between novel inflammatory markers derived from high-sensitivity C-reactive protein and heart failure: a cross-sectional study. BMC Cardiovasc Disord. 2025 Feb 18;25(1):111.
Zhu M, Ma Z, Zhang X, Hang D, Yin R, Feng J, Xu L, Shen H. C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis. BMC Med. 2022 Sep 19;20(1):301.
Burger PM, Koudstaal S, Mosterd A, Fiolet ATL, Teraa M, van der Meer MG, Cramer MJ, Visseren FLJ, Ridker PM, Dorresteijn JAN., UCC-SMART study group. C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease. J Am Coll Cardiol. 2023 Aug 01;82(5):414-426.
Luo YF, Cheng ZJ, Wang YF, Jiang XY, Lei SF, Deng FY, Ren WY, Wu LF. Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis. BMC Geriatr. 2024 Mar 04;24(1):222.
Lee Y, McKechnie T, Doumouras AG, Handler C, Eskicioglu C, Gmora S, Anvari M, Hong D. Diagnostic Value of C-Reactive Protein Levels in Postoperative Infectious Complications After Bariatric Surgery: a Systematic Review and Meta-Analysis. Obes Surg. 2019 Jul;29(7):2022-2029.
Johns I, Moschonas KE, Medina J, Ossei-Gerning N, Kassianos G, Halcox JP. Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study. Open Heart. 2018;5(2):e000849.
Berman M, Ben-Ami R, Berliner S, Anouk M, Kaufman I, Broyde A, Borok S, Elkayam O. The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature. Life (Basel). 2021 Mar 20;11(3)
Amezcua-Castillo E, González-Pacheco H, Sáenz-San Martín A, Méndez-Ocampo P, Gutierrez-Moctezuma I, Massó F, Sierra-Lara D, Springall R, Rodríguez E, Arias-Mendoza A, Amezcua-Guerra LM. C-Reactive Protein: The Quintessential Marker of Systemic Inflammation in Coronary Artery Disease-Advancing toward Precision Medicine. Biomedicines. 2023 Sep 02;11(9)
Guo L, Huang Y, He J, Li D, Li W, Xiao H, Xu X, Zhang Y, Wang R. Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014. Sci Rep. 2024 Jun 11;14(1):13444.
Lopez-Roblero A, Serrano-Guzmán E, Guerrero-Báez RS, Delgado-Enciso I, Gómez-Manzo S, Aguilar-Fuentes J, Ovando-Garay V, Hernández-Ochoa B, Quezada-Cruz IC, Lopez-Lopez N, Canseco-Ávila LM. Single-nucleotide polymorphisms in the promoter of the gene encoding for C-reactive protein associated with acute coronary syndrome. Biomed Rep. 2024 Nov;21(5):150.
Figueroa-Hall LK, Xu B, Kuplicki R, Ford BN, Burrows K, Teague TK, Sen S, Yeh HW, Irwin MR, Savitz J, Paulus MP. Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors. Transl Psychiatry. 2022 Jul 12;12(1):279.
Bhardwaj N, Ahmed MZ, Sharma S, Nayak A, Anvikar AR, Pande V. C-reactive protein as a prognostic marker of Plasmodiumfalciparum malaria severity. J Vector Borne Dis. 2019 Apr-Jun;56(2):122-126.
Vuong NL, Le Duyen HT, Lam PK, Tam DTH, Vinh Chau NV, Van Kinh N, Chanpheaktra N, Lum LCS, Pleités E, Jones NK, Simmons CP, Rosenberger K, Jaenisch T, Halleux C, Olliaro PL, Wills B, Yacoub S. C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study. BMC Med. 2020 Feb 17;18(1):35.
de Souza Pires-Neto O, da Silva Graça Amoras E, Queiroz MAF, Demachki S, da Silva Conde SR, Ishak R, Cayres-Vallinoto IMV, Vallinoto ACR. Hepatic TLR4, MBL and CRP gene expression levels are associated with chronic hepatitis C. Infect Genet Evol. 2020 Jun;80:104200.