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Biomedical subjects

G Matic

Publications and source records attributed to G Matic.

6 recordsLinked to original sources

Background and indications for protein A-based extracorporeal immunoadsorption.

Protein A (SPA), a major cell wall component of Staphylococcus aureus, has occupied numerous investigators from its discovery in the late fifties. Its availability and avid binding to human immunoglobulins have led to extensive usage for diagnostic and research purposes. Today, SPA-based extracorporeal immunoadsorption relies on two rather different systems, namely, SPA-silica (Prosorba), and SPA-Sepharose (Immunosorba). Both systems are approved by the Food and Drug Administration for the core indications of rheumatoid arthritis and idiopathic thrombocytopenic purpura (SPA-silica) or hemophilia with inhibitors (SPA-Sepharose). Off label indications include immune disorders with a conceivable connection between autoantibody titers and disease activity, like forms of glomerulonephritis, systemic lupus erythematodes, myasthenia, and the Guillain-Barré syndrome as well as alloantibody formation in the context of e.g., transplantation. This review summarizes historical developments and important properties of SPA. Indications for extracorporeal therapy are discussed on the basis of available information and personal experience.

Adsorption↗

Three cases of C-ANCA-positive vasculitis treated with immunoadsorption: possible benefit in early treatment.

Wegener's granulomatosis is a vasculitic disease predominantly affecting the upper respiratory tract, lungs, and kidneys. Three patients with Wegener's granulomatosis and rapidly progressive glomerulonephritis were treated with an intensified regimen of immunoadsorption (IA) (Excorim or Therasorb) in addition to cyclophosphamide (CYC) and methylprednisolone (PRE). Patient A had been in remission under oral CYC/PRE. The first exacerbation was treated successfully with 4 IA treatments without changing medication. Patient B experienced 3 flares within 1 year, which were treated with 28 IA (3-7 IAs/course), intravenous CYC after each course, and PRE. A fall of creatinine levels from 120 to 190 micromol/L to 100 micromol/L was noted after IA and before administration of CYC. Patient C presented in uremia. Autoantibodies were eliminated by 11 IA treatments parallel to CYC/PRE therapy. They remained within a normal range for >1 year's follow-up; however, kidney function did not return. In conclusion, the observations in Patients A and B suggest a beneficial therapeutic effect of early IA in WG.

Adult↗

Removal of immunoglobulins by a protein A versus an antihuman immunoglobulin G-based system: evaluation of 602 sessions of extracorporeal immunoadsorption.

Elimination of IgG can be achieved by extracorporeal immunoadsorption (IA) based on specific binding to either staphylococcal protein A (Excorim) or sheep polyclonal antibodies directed against human IgG (Therasorb). In 602 analyzed sessions of IA, elimination of IgG was 60% through 80% depending on the treated plasma volume, with no significant difference between the mentioned systems. However, the decrease of IgM and IgA was approximately 50% in the anti-IgG compared to 20-40% in the protein A system. Plasma albumin concentration decreased by 20% in the anti-IgG system compared to 15% in the protein A system, and hemoglobin values increased by 2% in the anti-IgG system and decreased by 6% in the protein A system. In conclusion, a clinical relevance for these findings cannot be ruled out, and the individual choice might depend on the clinical situation and laboratory findings.

Antibodies, Anti-Idiotypic↗

Development of a DNA immunoadsorbent: coupling DNA on sepharose 4FF by an efficient activation method.

To remove anti-DNA antibodies from a patient's plasma with systemic lupus erythematosus (SLE), a DNA immunoadsorbent was developed by covalently coupling calf thymus DNA on activated Sepharose 4FF. Sepharose 4FF was activated with 5-norbornene-2,3-dicarboximido carbonochloridate (Cl-CO-ONB), which was proven to be a very effective method for preparation of affinity chromatographic adsorbents. The activation was carried out in dry acetone using 4-(dimethylamine)pyridine (DMAP) and triethylamine (TEA) as catalysts at 4 degrees C or at room temperature. The coupling of DNA to the activated support was investigated as a function of pH, temperature, time, concentration of DNA, and activation level. It was found that the pH for optimal coupling is 3.0, and the amount of coupled DNA increases with an increase either in the concentration of DNA or the activation level. The maximum amount of coupled DNA could reach 1.0 mg DNA/ml support. The incubation of 5 to 20 ml of SLE plasma with 1.0 ml of adsorbent resulted in an 80 to 90% decline in the anti-DNA antibody level. Nonspecific adsorption for normal IgG and total protein is less than 15%.

Acetone↗

Extracorporeal removal of circulating immune complexes: from non-selective to patient-specific.

The classical immune complex-mediated disease, termed serum sickness, developed a short time after the injection of horse anti-tetanus toxin. Antibodies against circulating horse plasma proteins lead to the formation of immune complexes within the blood circulation (CIC). The inflammatory response, including systemic complement activation and vasculitis, seriously affected the function of all organs, including the most susceptible kidney. Meanwhile CIC have been detected in almost every systemic disease, including autoimmune disorders and also cancer and infections. This brief review will focus on the rationale and the equipment for extracorporeal elimination of CIC.

Antigen-Antibody Complex↗