Low levels of plasma soluble complement receptor type 1 in patients receiving thrombolytic therapy for acute myocardial infarction

Karthikeyan, Ganesan; Baalasubramanian, Sivasankar; Seth, Sandeep; Das, Nibhriti

doi:10.1007/s11239-006-9040-5

Cited by 5 publications

(5 citation statements)

References 18 publications

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“…Despite the important role of the complement system in cardiovascular diseases 46 , 47 such as atherosclerosis 48 , 49 , myocardial infarction 50 , 51 , and acute ischaemic stroke 52 , no correlation between CR1 levels and LVEF was found. This finding corroborates with data from a study on patients with acute myocardial infarction 53 .…”

Section: Discussionsupporting

confidence: 91%

Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

Sandri

Lidani

Andrade

et al. 2018

Sci Rep

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Complement is an essential element in both innate and acquired immunity contributing to the immunopathogenesis of many disorders, including Chagas Disease (CD). Human complement receptor 1 (CR1) plays a role in the clearance of complement opsonized molecules and may facilitate the entry of pathogens into host cells. Distinct CR1 exon 29 variants have been found associated with CR1 expression levels, increased susceptibility and pathophysiology of several diseases. In this study, CR1 plasma levels were assessed by ELISA and CR1 variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD patients and 104 healthy controls. CR1 levels were significantly decreased in CD patients compared to controls (p < 0.0001). The CR1 rs1704660G, rs17047661G and rs6691117G variants were significantly associated with CD and in high linkage disequilibrium. The CR1*AGAGTG haplotype was associated with T. cruzi infection (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1*AGGGTG was related to the risk of chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113). This is the first study that provides insights on the role of CR1 in development and clinical presentation of chronic CD.

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Section: Discussionsupporting

confidence: 91%

Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

Sandri

Lidani

Andrade

et al. 2018

Sci Rep

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“…Enhanced susceptibility of that site to cleavage could lead to less regulation of complement on the surface of host cells while a decrease in the release of the soluble form could lead to lower regulation of the cascade in the fluid state. Elevated levels of plasma sCR1 have been reported in some diseases [ 59 ], but lower levels were found in other conditions [ 60 ]. In a small cohort of patients (171) Daborg and colleagues reported a slight elevation in CR1 in cerebrospinal fluid of individuals with AD or MCI that developed AD relative to controls plus those with MCI that had not advanced to AD [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Putative Role of CR1 in Alzheimer’s Disease: Genetic Association, Expression and Function

et al. 2016

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Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer’s disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved.

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“…This included both monomeric and dimeric forms of C3b, and the results are summarized in Table 1. Soluble CR1 (sCR1) refers to the entire extracellular domain of CR1 (Figure 1) and usually describes a form derived recombinantly, since levels of endogenous sCR1 produced by proteolytic shedding from the cell surface are very low [21]. Despite some variation in the experimental results due to the nature of the techniques employed, it is evident that CR1 binds to dimeric C3b with low nanomolar affinity (Table 1).…”

Section: General and Comparativementioning

confidence: 99%

The Molecular Mechanisms of Complement Receptor 1—It Is Complicated

Hardy,

Mansour,

Rowe

et al. 2023

Biomolecules

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Human complement receptor 1 (CR1) is a membrane-bound regulator of complement that has been the subject of recent attempts to generate soluble therapeutic compounds comprising different fragments of its extracellular domain. This review will focus on the extracellular domain of CR1 and detail how its highly duplicated domains work both separately and together to mediate binding to its main ligands C3b and C4b, and to inhibit the classical, lectin, and alternative pathways of the complement cascade via the mechanisms of decay acceleration activity (DAA) and co-factor activity (CFA). Understanding the molecular basis of CR1 activity is made more complicated by the presence not only of multiple ligand binding domains within CR1 but also the fact that C3b and C4b can interact with CR1 as both monomers, dimers, and heterodimers. Evidence for the interaction of CR1 with additional ligands such as C1q will also be reviewed. Finally, we will bring the mechanistic understanding of CR1 activity together to provide an explanation for the differential complement pathway inhibition recently observed with CSL040, a soluble CR1-based therapeutic candidate in pre-clinical development.

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Low levels of plasma soluble complement receptor type 1 in patients receiving thrombolytic therapy for acute myocardial infarction

Abstract: Plasma sCR1 levels are reduced in patients receiving thrombolysis for AMI. Replenishing plasma sCR1 might limit complement-mediated injury in this setting.

Cited by 5 publications

References 18 publications

Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

Analysis of the Putative Role of CR1 in Alzheimer’s Disease: Genetic Association, Expression and Function

The Molecular Mechanisms of Complement Receptor 1—It Is Complicated

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