Immunosorbent technique of blood purification

  Immunosorbent therapy is a new technique developed in the last 20 years. It combines highly specific antigens, antibodies or certain substances with specific physical and chemical affinity (ligands) with adsorbent materials (carriers) to make adsorbents (columns), and uses their specific adsorption properties to selectively or relatively specifically remove endogenous pathogenic factors from patients’ blood to achieve the purpose of alleviating the disease.  (a) Immunosorbent classification 1, bioaffinity type: (1) antigen-antibody binding type: refers to the antigen (antigen fixed type) or antibody (antibody fixed type) fixed on the carrier made of adsorption column; (2) complement binding type: fixed C1q, using its characteristics of binding immune complex Fc segment, adsorption of immune complexes in the blood; (3) Fc segment binding type: protein A as a ligand, adsorption of blood The Fc segment of IgG molecules in blood is adsorbed using protein A as the ligand. Biophilic adsorbents are highly specific, but the supply of raw materials, preparation and purification, sterilization and storage are difficult.  The former uses the electrostatic interaction between the adsorbent and specific substances to achieve the purpose of adsorption and removal of pathogenic substances; the latter uses the hydrophobic combination between the hydrophobic group of the side chain of the adsorbent and the adsorbed substance to achieve the purpose of adsorption and removal. The latter uses the hydrophobic bonding between the hydrophobic group of the side chain of the adsorbent and the adsorbed material to achieve adsorption and removal.  (ii) Immunosorbent treatment mechanism Immunosorbent can improve the immune status of the body directly by removing large molecules of pathogenic substances from the blood circulation. Its effect on the immune system is mainly: (1) humoral immunity: removal of autoantibodies or pathogenic antibodies, circulating immune complexes and inflammatory factors; removal of factors affecting coagulation and hemodynamics. (2) Cellular immunity: correction of CD4 /CD8 cell ratio, increase of CD25 cell ratio and reduction of self-activated T cells in patients with severe SLE.  (3) Advantages of immunosorbent versus plasma replacement (1) More selective: SPA is selective for the clearance of antibodies and immune complexes in plasma, with little effect on the coagulation system and normal plasma components, and does not affect the therapeutic effect of drugs. (2) High clearance efficiency and low adverse effects: the amount of antibodies cleared by single immunosorbent is 2-3 times higher than that of plasma replacement. (3) No need to replenish replacement fluid: it eliminates the possibility of transfusion reactions and various blood-borne infectious diseases. (4) More economical.  (4) Immunosorbent columns with relatively certain efficacy and now widely used: (1) Staphylococcal A protein (SPA) adsorbent column: a kind of Staphylococcus aureus cell wall protein with four highly homogeneous Fc binding regions at the amino terminus, which can bind to pathogenic antibodies in plasma, especially the Fc segment of IgG-type antibody molecules. The binding is reversible, the two are tightly bound at physiological pH and dissociate when the pH drops to 2,3-2,5, so it can be used repeatedly and is a commonly used immunosorbent. (2) DNA immunosorbent column: DNA is used as ligand, fixed on the carrier, made into adsorbent and adsorbent column, using antigen-antibody bioaffinity, adsorption to remove anti-DNA antibodies in the blood, mostly used in the treatment of SLE. (3) Anti-human low-density lipoprotein (LDL) adsorption column: specific removal of LDL from plasma, used in patients with hypercholesterolemia.  (5) Immunosorbent is mainly applied to the following diseases 1. Severe SLE: Immunosorbent therapy can rapidly remove autoantibodies and CIC in patients in a short period of time, improve the damage to vital organs caused by autoantibodies or immune complex-mediated inflammation, and control lupus activity. Studies have proved that hormones and CTX inhibit lymphocytes from producing DNA antibodies, and immunosorbent can rapidly remove the DNA antibodies already produced.  2, primary and recurrent focal segmental glomerulosclerosis: there is a circulating infiltration factor in these patients, which plays an important role in the pathological process of the disease. Immunosorbent is effective in patients with hormone sensitivity.  3. anti-neutrophil cytoplasmic antibody-associated vasculitis 4. neurological disorders: patients with myasthenia gravis have anti-acetylcholine receptor antibodies in their serum, which interfere with neuromuscular transmission and lead to muscle weakness. Immunosorbent can remove the antibody and rapidly improve the symptoms of myasthenia gravis. The levels of serum IgG, fibrinogen and complement C3 all decreased. The presence of autoantibodies against peripheral nerve tissue in patients with Guillain-Barre syndrome can lead to rapid recovery by immunosorbency. It has also been reported that IA can be effective in the treatment of acute infectious polyneuritis.  5. Dilated cardiomyopathy: In patients with dilated cardiomyopathy, a variety of different autoantibodies have been detected, such as: cardiac myosin antibodies, cardiac β1 2 adrenergic receptor antibodies, muscarinic M2 receptor antibodies, etc. Patients receiving immunosorbent therapy not only have improved left ventricular ejection fraction and decreased left ventricular end-diastolic and end-systolic volumes, but also have significantly improved their quality of life.  6, kidney transplantation-related diseases: ① pre-transplantation: for patients with hypersensitive immune status, the application of immunosorbent rapidly removes anti-HLA antibodies, reduces the rate of group reactive antibody (PRA) positivity, alleviates rejection and improves kidney survival rate. ②Post-transplantation: When rejection occurs and graft function deteriorates, intensive treatment with immunosorbent combined with anti-rejection drugs can be used to reverse the rejection reaction. ③For transplantation with ABO blood group incompatibility, A/B antibodies can be cleared by immunosorbent before transplantation, and the anti-A/B antibody level can be controlled at a lower level for a longer period of time after transplantation.  7. Other potentially effective diseases: from the perspective of autoantibody clearance, immunosorbent therapy can be used for the treatment of various autoimmune diseases, such as antiglomerular basement membrane disease, lipoprotein nephropathy, Wegener’s granulomatosis, type II cryoglobulinemia, rheumatoid arthritis, immune thrombocytopenic purpura, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, anticoagulant antibody-mediated coagulation abnormalities, etc.