Full-Range CRP: Going beyond a diagnostic tool?

In-vitro diagnostics (IVDs) refer to clinical tests done on samples that are retrieved from a patient, which are then processed and analyzed in a lab. With recent advancements in technology propelling the constant innovation of treatment strategies in the medical field, it is no longer uncommon clinical practice to see clinicians ordering IVD lab tests in conjunction with conventional methods of diagnosis, thus resulting in more precise diagnoses with the added perk of sharpening medical acumen.

What are IVDs ?

In-vitro diagnostics (IVDs) refer to clinical tests done on samples that are retrieved from a patient, which are then processed and analyzed in a lab. With recent advancements in technology propelling the constant innovation of treatment strategies in the medical field, it is no longer uncommon clinical practice to see clinicians ordering IVD lab tests in conjunction with conventional methods of diagnosis, thus resulting in more precise diagnoses with the added perk of sharpening medical acumen.

A constantly-growing use trend over the last decade can be observed for IVDs and the trend seems to show no signs of slowing down. The IVD market blankets a broad range of tools, ranging from simple pregnancy kits and glucose strips, to intricate diagnostic lab testing, such as immunoassays or hematology analyzers. These sophisticated testing devices make use of a multitude of different technologies in order to accurately isolate and detect different biomarkers to aid in screening and diagnosis. One such biomarker is the C-reactive protein.

What- is C-reactive protein (CRP) ?

C-reactive protein (CRP) is an acute-phase cyclic pentameric protein produced by the liver and is a commonly assayed biomarker usually attributed to acute inflammation in the body. The primary cause of CRP level increase is due to elevated concentrations of interleukin-6 (IL-6) in the plasma. In cases of acute inflammation, CRP serum levels usually rise rapidly and peak within 48 hours, with a widely-agreed-upon consensus that sharp increases in CRP levels are routinely associated with nonspecific acute-phase inflammation. [1]

Recent studies suggest that hs-CRP has also been shown to be representative of certain chronic illnesses. An increased risk of cardiovascular disease has been characterized by low levels of CRP detected using hs-CRP technologies, which may point to underlying atherosclerosis. On that note, prior studies as well as guidelines [2] imply that FR-CRP (CRP + hs-CRP) is not only crucial in determining acute-phase inflammatory events, but may also be indispensable as a predictive tool for chronic cardiovascular and neurodegenerative diseases.

Despite the habitual application of CRP in the screening of inflammatory conditions, certain interesting properties of the pentameric protein have also led to other avenues of CRP significance being pursued. This dive into the clinical implications of CRP has also revealed it to be a crucial factor in the mediation of inflammation, with sufficient evidence that links CRP to the onset of the abovementioned diseases.

Pentameric CRP (pCRP)

Pentameric CRP (pCRP) exists as an annular structure made up of five identical subunits, but can undergo an oxidation-reduction reaction, leading to a primary structural change from pCRP to pCRP*, before undergoing dissociation into mCRP (monomeric CRP). The inflammation mediation process begins upon onset of insult, where the inflammation mediator Phospholipase A2 (PLA2) catalyses the cleavage of surface membrane glycerophospholipids at the sn-2 position, liberating fatty acids such as Arachidonic Acid and lysophospholipids, which then exposes the lysophosphatidylcholines (LPCs) on the surface membrane along with phosphocholine (pCH). The binding of pCRP subunits to pCH is what mediates this conformational change from a pentameric structure into monomers, functionally converting from a “systemic inflammatory marker” into a “response system activator”. This recent discovery of a “CRP-mediated inflammatory response system” has sparked new interest which may potentially lead to discovery of new forms of NSAIDS through the inhibition of CRP-mediated inflammation. [3]

Global use of CRP In the field of diagnostics has been trending upwards with the advent of the COVID-19 pandemic, with a healthy number of studies regarding CRP as an efficient and accessible tool in the management of COVID-19. These discoveries are indicative of even deeper diagnostic use for the C-reactive protein, which then begs the question, why are we not using as much CRP diagnostics as we should when it comes to infections or chronic inflammatory diseases?

Reference list:

[1]. Seo, Hong Seog. “The Role and Clinical Significance of High-Sensitivity C-Reactive Protein in Cardiovascular Disease.” Korean Circulation Journal, The Korean Society of Cardiology, Mar. 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318086/.

[2]. Arnett DK;Blumenthal RS;Albert MA;Buroker AB;Goldberger ZD;Hahn EJ;Himmelfarb CD;Khera A;Lloyd-Jones D;McEvoy JW;Michos ED;Miedema MD;Muñoz D;Smith SC;Virani SS;Williams KA;Yeboah J;Ziaeian B; “2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.” Journal of the American College of Cardiology, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/30894319/.

[3]. Caprio, Vittorio, et al. “PCRP-Mcrp Dissociation Mechanisms as Potential Targets for the Development of Small-Molecule Anti-Inflammatory Chemotherapeutics.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2018.01089/full.