C-Reactive Protein Triggers Cell Death in Ischemic Cells

Sheriff, Ahmed; Kayser, Stefan; Brunner, Patrizia; Vogt, Birgit

doi:10.3389/fimmu.2021.630430

Cited by 53 publications

(54 citation statements)

References 114 publications

(153 reference statements)

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“…Together with the complement components C1q-C4, C-reactive protein (CRP) functions in the disposal of bacteria and apoptotic or necrotic host cells [ 161 , 162 ]. As COVID-19 is characterized by high CRP levels, it was proposed that reduction of the CRP levels by therapeutic apheresis, might reduce the pathological process in early disease [ 163 ].…”

Section: Targeting Nets In Covid-19 Treatmentmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

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Section: Targeting Nets In Covid-19 Treatmentmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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“…C-reactive protein (CRP) is a well-established sensitive marker of inflammation. Regardless of that, a growing body of data has identified CRP as a direct mediator of inflammation and immune response (1). This less known role of CRP is based on two immunological functions: (a) activation of the classical complement pathway via C1q binding and (b) binding to immunoglobulin Fcγ receptors after opsonisation of biological particles (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study

Ries¹,

Torzewski

Heigl

et al. 2021

Front. Cardiovasc. Med.

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Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival.Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans.Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9–279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR).Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients.Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial.Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008988, DRKS00008988.

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“…So far, there is no pharmaceutical option to reduce the extremely high synthesis/level of CRP during an acute phase response, but the rapid reduction of high CRP levels in medium and severe courses of COVID-19 was proposed early on during the pandemic (21)(22)(23) and also recently (14,24).…”

Section: Introductionmentioning

confidence: 99%

“…CRP is an ancient antibody, being part of the innate immune response and increasing rapidly during the acute phase reaction. Increasing evidence suggests that CRP causally promotes tissue destruction during the inflammatory response under certain pathological circumstances ( 14 ). Intraalveolar edema and hemorrhage are a common observation in the lungs of COVID-19 patients, resulting in ischemic alveolar tissue.…”

Section: Introductionmentioning

confidence: 99%

Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase

Ringel¹,

Ramlow

Bock

et al. 2021

Front. Immunol.

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BackgroundPlasma levels of C-reactive protein (CRP), induced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) triggering COVID-19, can rise surprisingly high. The increase of the CRP concentration as well as a certain threshold concentration of CRP are indicative of clinical deterioration to artificial ventilation. In COVID-19, virus-induced lung injury and the subsequent massive onset of inflammation often drives pulmonary fibrosis. Fibrosis of the lung usually proceeds as sequela to a severe course of COVID-19 and its consequences only show months later. CRP-mediated complement- and macrophage activation is suspected to be the main driver of pulmonary fibrosis and subsequent organ failure in COVID-19. Recently, CRP apheresis was introduced to selectively remove CRP from human blood plasma.Case ReportA 53-year-old, SARS-CoV-2 positive, male patient with the risk factor diabetes type 2 was referred with dyspnea, fever and fulminant increase of CRP. The patient’s lungs already showed a pattern enhancement as an early sign of incipient pneumonia. The oxygen saturation of the blood was ≤ 89%. CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started immediately. CRP apheresis was performed via peripheral venous access on 4 successive days. CRP concentrations before CRP apheresis ranged from 47 to 133 mg/l. The removal of CRP was very effective with up to 79% depletion within one apheresis session and 1.2 to 2.14 plasma volumes were processed in each session. No apheresis-associated side effects were observed. It was at no point necessary to transfer the patient to the Intensive Care Unit or to intubate him due to respiratory failure. 10 days after the first positive SARS-CoV-2 test, CRP levels stayed below 20 mg/l and the patient no longer exhibited fever. Fourteen days after the first positive SARS-CoV-2 test, the lungs showed no sign of pneumonia on X-ray.ConclusionThis is the first report on CRP apheresis in an early COVID-19 patient with fulminant CRP increase. Despite a poor prognosis due to his diabetes and biomarker profile, the patient was not ventilated, and the onset of pneumonia was reverted.

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C-Reactive Protein Triggers Cell Death in Ischemic Cells

Cited by 53 publications

References 114 publications

Patients with COVID-19: in the dark-NETs of neutrophils

Patients with COVID-19: in the dark-NETs of neutrophils

C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study

Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase

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