C-reactive Protein in Inflammatory Diseases: Clinical Aspects

Topic Information

Dear Colleagues,

This Topic focuses on the clinical relevance of C-reactive protein. Most physicians are familiar with it as a diagnostic biomarker, but only a few have realised that it can be a pathomolecule. After all, biomarker is of course not a physiological function. The main task of CRP is to mark cells to be disposed of, which has been shown for decades in various animal models and has been broken down to the molecular level. For several decades, CRP has been established as an extremely sensitive, reliable and early indicator of inflammatory and tissue-destructive processes. Following an acute phase stimulus, up to 1000-fold increased values can be measured.

This prototype of the human acute phase protein has been considered an inflammatory marker since it was first described by Tillet and Francis in 1930.

However, the mere use of CRP as a readily measurable inflammation marker neglects the biological function of the protein.

CRP is a serum protein and a mediator of innate immunity. The diverse functions of CRP across all living species led to the conclusion that CRP is a prehistoric precursor of all antibodies in the evolutionarily much-later-appearing mammals.

Already in the horseshoe crab (Limulus), a “living fossil” at least 250 million years old, CRP forms immune complexes together with the complement system and thus assumes defence functions. At the same time, it acts phylogenetically as an antibody in numerous species, such as fish, which have no adaptive immune system. In humans, its functions are complex and part of re-intensified research.

It is now accepted, even if not everyone is aware of it, that CRP plays a central role in the development of inflammation-related tissue damage. CRP activates (in the manner of antibodies) the complement system via the classical pathway and macrophages via Fc receptors. Therefore, CRP, in the manner of antibodies, binds to Fc receptors.

The present Topic aims to provide an overview of relevant studies and provide an outlook into the future perspective on this pivotal protein. This will not only provide valuable information on the potential for CRP-driven prognostic decisions, but also identify obstacles that need to be overcome to address CRP therapeutically.

Dr. Ahmed Sheriff
Prof. Dr. Jan Torzewski
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	14.7 Days	CHF 2600	Submit
Clinics and Practice clinpract	2.3	2.0	2011	26.4 Days	CHF 1600	Submit
Diagnostics diagnostics	3.6	3.6	2011	18.8 Days	CHF 2600	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	19.7 Days	CHF 2600	Submit
Pharmaceuticals pharmaceuticals	4.6	4.7	2004	15.7 Days	CHF 2900	Submit

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All Biomedicines Clinics and Practice Diagnostics JCM Pharmaceuticals

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Open AccessPerspective

Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option

by

Ahmed Sheriff

,

Rudolf Kunze

,

Patrizia Brunner

and

Birgit Vogt

Biomedicines 2023, 11(8), 2279; https://doi.org/10.3390/biomedicines11082279 - 16 Aug 2023

Viewed by 497

Abstract

In medicine, C-reactive protein (CRP) has become established primarily as a biomarker, predicting patient prognosis in many indications. Recently, however, there has been mounting evidence that it causes inflammatory injury. As early as 1999, CRP was shown to induce cell death after acute [...] Read more.

In medicine, C-reactive protein (CRP) has become established primarily as a biomarker, predicting patient prognosis in many indications. Recently, however, there has been mounting evidence that it causes inflammatory injury. As early as 1999, CRP was shown to induce cell death after acute myocardial infarction (AMI) in rats and this was found to be dependent on complement. The pathological effect of CRP was subsequently confirmed in further animal species such as rabbit, mouse and pig. A conceptual gap was recently closed when it was demonstrated that ischemia in AMI or ischemia/hypoxia in the severe course of COVID-19 causes a drastic lack of energy in involved cells, resulting in an apoptotic presentation because these cells cannot repair/flip-flop altered lipids. The deprivation of energy leads to extensive expression on the cell membranes of the CRP ligand lysophosphatidylcholine. Upon attachment of CRP to this ligand, the classical complement pathway is triggered leading to the swift elimination of viable cells with the appearance of an apoptotic cell by phagocytes. They are being eaten alive. This, consequently, results in substantial fibrotic remodeling within the involved tissue. Inhibiting this pathomechanism via CRP-targeting therapy has been shown to be beneficial in different indications. Full article

(This article belongs to the Topic C-reactive Protein in Inflammatory Diseases: Clinical Aspects)

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Open AccessArticle

Discrepancy of C-Reactive Protein, Procalcitonin and Interleukin-6 at Hospitalization: Infection in Patients with Normal C-Reactive Protein, Procalcitonin and High Interleukin-6 Values

by

Eun-Hwa Lee

,

Kyoung-Hwa Lee

,

Young-Goo Song

and

Sang-Hoon Han

J. Clin. Med. 2022, 11(24), 7324; https://doi.org/10.3390/jcm11247324 - 09 Dec 2022

Cited by 2 | Viewed by 1386

Abstract

C-reactive protein (CRP) or procalcitonin (PCT) alone has limitations in the early detection of infection or inflammation due to shortcomings in specificity and varied cut-off values. Recently, interleukin (IL)-6 has been assessed, but it is not known to what extent the three values [...] Read more.

C-reactive protein (CRP) or procalcitonin (PCT) alone has limitations in the early detection of infection or inflammation due to shortcomings in specificity and varied cut-off values. Recently, interleukin (IL)-6 has been assessed, but it is not known to what extent the three values are homogeneous in reality. This retrospective study was conducted with two large datasets (discrepancy set with results within 24 h of admission [7149 patients] and follow-up set until 2 weeks of hospital stay [5261 tests]) consisting of simultaneous examinations of CRP, PCT, and IL-6 between January 2015 and August 2021. The specific discrepant group (n = 102, 1.4%) with normal CRP (<10 mg/L) and PCT (<0.1 ng/mL) and high IL-6 (≥100 pg/mL) values was extracted from the discrepancy set. Dimensionality reduction and visualization were performed using Python. The three markers were not clearly clustered after t-distributed stochastic neighbor embedding. Pearson’s correlation coefficients between two markers were substantially low (0.23–0.55). Among the high normalized IL-6 levels (≥0.5) (n = 349), 17.8% and 38.7% of CRP and PCT levels were very low (≤0.01). 9.2% and 13.4% of normal CRP (n = 1522) had high PCT (≥0.5 ng/mL) and IL-6 (≥100 pg/mL) values, respectively. Infection and bacteremia among 102 patients occurred in 36 (35.3%) and 9 (8.8%) patients, respectively. In patients with bacteremia, IL-6 was the first to increase, followed by PCT and CRP. Our study revealed that CRP, PCT, and IL-6 levels were considerably discrepant, which could be misinterpreted if only CRP tests are performed. Full article

(This article belongs to the Topic C-reactive Protein in Inflammatory Diseases: Clinical Aspects)

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Open AccessArticle

Sustainability of C-Reactive Protein Apheresis in Acute Myocardial Infarction—Results from a Supplementary Data Analysis of the Exploratory C-Reactive Protein in Acute Myocardial Infarction-1 Study

by

Horst Skarabis

,

Jan Torzewski

,

Wolfgang Ries

,

Franz Heigl

,

Christoph D. Garlichs

,

Rudolf Kunze

and

Ahmed Sheriff

J. Clin. Med. 2022, 11(21), 6446; https://doi.org/10.3390/jcm11216446 - 31 Oct 2022

Cited by 2 | Viewed by 1260

Abstract

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) [...] Read more.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3–9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS). Compared with the control group (n = 34), cardiac damage was significantly lower in the apheresis group (n = 32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65–177) d whether the effect of CRP apheresis is clinically maintained. After this time period, wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of <0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of >0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (−5.4%; p = 0.05), a better LVEF (+6.4%; p = 0.03), and an improved CS (−6.1%; p = 0.005). No significant improvement, however, was observed for LS (−2.9%; p = 0.1). These data suggest a sustained positive effect of CRP apheresis on heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue. Full article

(This article belongs to the Topic C-reactive Protein in Inflammatory Diseases: Clinical Aspects)

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