A redox sensitivity-based method to quantify both pentameric and monomeric C-reactive protein in a single assay

Yao, Zhenyu; Zhang, Yanmin; Potempa, Lawrence A.; Rajab, Ibraheem M.; Ji, Lianxing; Lv, Jian-Min; Liu, Shanhui; Zhang, Lin; Wu, Haibin

doi:10.1016/j.jim.2019.04.009

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…When pCRP binds to an activated membrane, biochemical forces contribute to dissociation of the pentamer which induces a pronounced structural rearrangement exposing a cryptic binding site on the dissociated CRP subunits for cholesterol molecules found in lipid rafts. Dissociated CRP subunits are described as "monomeric, modified" CRP (i.e., abbreviated as "mCRP") (11)(12)(13)(14)(15)(16). The mCRP isoform is antigenically distinctive from the pCRP isoform and has significantly reduced aqueous solubility.…”

Section: Introductionmentioning

confidence: 99%

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression

2020

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C-reactive protein (CRP) is a widely known, hepatically synthesized protein whose blood levels change rapidly and pronouncedly in response to any tissue damaging event associated with an inflammatory response. The synthesis and secretion of CRP is stimulated by interleukin-6, an early pleiotropic cytokine released by macrophages, endothelial, and other cells that are activated when localized normal tissue structures are compromised by trauma or disease. Serum CRP levels can change rapidly and robustly from 10-100-fold within 6-72 h of any tissue damaging event. Elevated blood levels correlate with the onset and extent of both activated inflammation and the acute phase biochemical response to the tissue insult. Because its functional bioactivity as the prototypic acute phase reactant has eluded clear definition for decades, diagnosticians of various conditions and diseases use CRP blood levels as a simple index for ongoing inflammation. In many pathologies, which involves many different tissues, stages of disease, treatments, and responses to treatments, its interpretive diagnostic value requires a deeper understanding of the localized tissue processes and events that contribute signals which regulate protective or pathological host defense bioactivities. This report presents concepts that describe how local tissue activation events can lead to a non-proteolytic, conformational rearrangement of CRP into a unique isoform with distinctive solubility, antigenicity, binding reactivities and bioactivities from that protein widely known and measured in serum. By describing factors that control the expression, tissue localization, half-life and pro-inflammatory amplification activity of this CRP isoform, a unifying explanation for the diagnostic significance of CRP measurement in disease is advanced.

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Section: Introductionmentioning

confidence: 99%

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression

2020

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“…This monomer could not be re-associated back into its pentameric form, the dissociation being accompanied by significant changes in both structure and function (26). On the basis of reduction of the intrachain disulphide in this mCRP, but not in pCRP, by reducing agents such as dithiothreitol, several reports have shown discrimination between pentameric and monomeric CRP (21,27,28).…”

Section: Introductionmentioning

confidence: 92%

“…Several models suggesting a physiological mechanism for the formation of mCRP have been postulated within the literature. The most widely accepted involves dissociation through calciumdependent binding of pCRP to cell membranes (17,18,25,(27)(28)(29)(30)(31)(32) although a clear picture is yet to emerge of the nature and fate of the resulting mCRP conformer. Binding to microvesicles has been proposed to lead to pCRP structural changes that allow binding of C1q and hence complement activation (27).…”

Section: Introductionmentioning

confidence: 99%

Monomeric C-Reactive Protein in Serum With Markedly Elevated CRP Levels Shares Common Calcium-Dependent Ligand Binding Properties With an in vitro Dissociated Form of C-Reactive Protein

et al. 2020

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“…The property as acute-phase reactant has long been exploited for clinical purposes. CRP is a dynamic protein that undergoes conformational changes between circulating native pentameric CRP (pCRP), pentameric symmetrical forms (pCRP*) and monomeric (or modified) CRP (mCRP) forms (3)(4)(5)(6)(7)(8)(9)(10). It is thought that pCRP can dissociate into mCRP through pCRP* (8,10,11).…”

Section: Introductionmentioning

confidence: 99%

mCRP as a Biomarker of Adult-Onset Still’s Disease: Quantification of mCRP by ELISA

et al. 2022

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BackgroundC-reactive protein (CRP) is a dynamic protein that undergoes conformational changes between circulating native pentameric CRP (pCRP), pentameric symmetrical forms (pCRP*) and monomeric (or modified) CRP (mCRP) forms. mCRP exhibits strong pro-inflammatory activity and activates platelets, leukocytes, and endothelial cells. Abundant deposition of mCRP in inflamed tissues plays a role in several disease conditions, such as ischemia/reperfusion injury, Alzheimer’s disease, and cardiovascular disease. Although pCRP is typically quantified rather than mCRP for clinical purposes, mCRP may be a more appropriate disease marker of inflammatory diseases. Therefore, simple methods for quantifying mCRP are needed.MethodsWe developed a specific enzyme-linked immunosorbent assay (ELISA) to measure plasma levels of mCRP. Plasma mCRP concentration was measured in patients with adult-onset Still’s disease (AOSD) (n=20), polymyalgia rheumatica (PMR) (n=20), rheumatoid arthritis (RA) (n=30), infection (n=50), and in control subjects (n=30) using the developed ELISA.ResultsWe demonstrated that mCRP is elevated in some inflammatory autoimmune diseases, particularly AOSD. The mCRP concentration was also significantly higher among AOSD patients than RA, PMR patients and controls (477 ng/ml, 77 ng/ml, 186 ng/ml, and 1.2 ng/ml, respectively). Also, the mCRP (×1,000)/pCRP ratio was significantly higher among AOSD patients than RA, PMR, and infection patients (3.5, 0.6, 1,6, and 2.0, respectively).ConclusionThe plasma mCRP levels are elevated in some autoimmune diseases, particularly AOSD. The plasma mCRP levels may therefore be a potentially useful biomarker for AOSD.

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A redox sensitivity-based method to quantify both pentameric and monomeric C-reactive protein in a single assay

Cited by 7 publications

References 35 publications

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression

Monomeric C-Reactive Protein in Serum With Markedly Elevated CRP Levels Shares Common Calcium-Dependent Ligand Binding Properties With an in vitro Dissociated Form of C-Reactive Protein

mCRP as a Biomarker of Adult-Onset Still’s Disease: Quantification of mCRP by ELISA

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