PentraSorb C‐Reactive Protein: Characterization of the Selective C‐Reactive Protein Adsorber Resin

Abstract

C‐reactive protein (CRP) is well known as a general marker of inflammation. It furthermore represents a reliable risk factor for cardiac events and mediates tissue damage in acute myocardial infarction (AMI). It has been demonstrated that selective CRP depletion by extracorporeal apheresis in a porcine AMI model had beneficial effects on the infarcted area and the cardiac output. We therefore developed a novel adsorber for CRP apheresis from human plasma (PentraSorb CRP). It is intended for use in the clinic as therapy for patients suffering from AMI or other acute inflammatory diseases with elevated CRP plasma levels. The PentraSorb resin specifically bound CRP from human blood plasma and almost no other proteins as determined via Sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS‐PAGE). The resin further efficiently and selectively depleted CRP from plasma with low as well as high CRP concentrations (10–100 mg/L) at different flow rates, ranging from 17 to 40 mL/min. The resin was regenerable for up to 200 times without losing its CRP binding capacity or affecting biocompatibility. The depletion of CRP from plasma was comparable between the utilized small‐scale column (0.5 mL resin) and the PentraSorb CRP adsorber (20 mL resin volume). The established features can therefore be applied to the clinical setting. In summary, PentraSorb CRP provides a novel, specific, and efficient CRP‐binding resin that could be used in apheresis therapy for patients suffering from inflammatory diseases such as AMI, stroke, acute pancreatitis, and Crohn's disease.

C-Reactive Protein Causes Blood Pressure Drop in Rabbits and Induces Intracellular Calcium Signaling

“…Human plasma samples were collected from patients with high CRP concentrations, pooled and stored frozen at −20°C until the experiments began. Plasma pool was thawed, and CRP was purified by running an affinity chromatography column of a selective CRP-binding matrix (Pentracor GmbH, Germany) ( 24 ). Elution of CRP was performed by an elution buffer consisting of 0.1 M Tris, 0.2 M NaCl, and 2 mM EDTA, pH 8, which inhibited the Ca 2+ -dependent binding of CRP to the matrix.…”

Selective C‐Reactive Protein‐Apheresis in Patients

“…For CRP‐apheresis, a regenerative single‐adsorber‐system has been implemented (PentraSorb CRP; Pentracor GmbH, Hennigsdorf, Germany). The CRP adsorber contains a PC‐derivative as ligand for CRP linked to 20 mL of an agarose‐based resin . The apheresis is performed in cycles, alternating between loading of the adsorber with patient plasma and regeneration, which follows a fixed sequence of washing solutions (≥100 mL NaCl, ≥60 mL glycine/HCl, ≥ 80 mL PBS, and ≥ 80 mL NaCl).…”

“…Our new adsorber was developed for selective removal of CRP from human plasma. In the adsorber, CRP specifically binds to a phosphocholine (PC)‐ligand in an extracorporeal circuit . A few years ago, we showed in a porcine model of acute myocardial infarction that selective CRP‐apheresis significantly reduces CRP plasma levels in animals .…”

C‐Reactive Protein: From Biomarker to Trigger of Cell Death?

“…The research group of Sheriff and the company Pentracor GmbH developed a CRP‐specific adsorber (PentraSorb CRP) and established this new therapeutic approach of selective CRP apheresis . The adsorber has been clinically tested for its safety and performance in patients with AMI .…”