Sedlacek H H, Gronski P, Hofstaetter T, Kanzy E J, Schorlemmer H U, Seiler F R
Klin Wochenschr. 1983 Aug 1;61(15):723-36. doi: 10.1007/BF01497399.
Antibodies of the IgG class possess antibacterial, antiviral and toxin neutralizing properties and for this reason are administered prophylactically and therapeutically. In the case of the immunoglobulin preparations commercially available for i.v. application a basic distinction must be made between unsplit immunoglobulins and those antibody preparations obtained by enzymatic digestion, such as F(ab')2 or Fab antibodies. This survey deals with the largely experimental evidence describing the biological properties of these preparations. Administration of antibodies in the presence of the corresponding antigens leads to the formation of immune complexes in the organism. These immune complexes can activate, either directly or indirectly, the cellular and humoral systems which are involved in phagocytosis and the elimination of antigens, in the regulation of the body's own antibody production and in inflammatory reactions. As a result of their inability to interact with Fc receptors, immune complexes with F(ab')2 or F(ab) antibodies appear to be less active in the release of inflammation mediators from leucocytes and thrombocytes than immune complexes with unsplit immunoglobulins. These, on the other hand, can antigen-specifically and non-antigen-specifically suppress the immune system which is not the case for immune complexes with F(ab')2 or Fab antibodies. There are indications that these split products also occur in vivo due to the action of tissue and leucocyte proteases. Unlike Fab preparations, F(ab')2 antibodies have antibacterial and antiviral potencies similar to unsplit immunoglobulins, which is probably due to the ability of F(ab')2 molecules to activate complement, not by the classical but by the alternative pathway. Like Fab preparations, F(ab')2 molecules appear to be superior to unsplit IgG in the elimination of haptens. On account of the relatively long period of time unsplit immunoglobulins remain in the blood, they are well suited for prophylactic treatment and substitution over longer periods. The extent to which indications, obtained predominantly from experimental studies, of a reduced release of inflammation mediators, a lack of immune suppression and a lack of augmentation of IgG catabolism would advocate the use of F(ab')2 split products, especially for therapeutic purposes, can only be ascertained after prospective and comparative studies have been carried out.
IgG类抗体具有抗菌、抗病毒和毒素中和特性,因此可用于预防性和治疗性给药。就市售的静脉内应用免疫球蛋白制剂而言,必须在未裂解的免疫球蛋白与通过酶消化获得的抗体制剂(如F(ab')2或Fab抗体)之间做出基本区分。本综述涉及描述这些制剂生物学特性的大量实验证据。在相应抗原存在的情况下给予抗体可导致机体中免疫复合物的形成。这些免疫复合物可直接或间接激活参与吞噬作用和抗原清除、机体自身抗体产生调节以及炎症反应的细胞和体液系统。由于其无法与Fc受体相互作用,与F(ab')2或F(ab)抗体形成的免疫复合物在从白细胞和血小板释放炎症介质方面似乎不如与未裂解免疫球蛋白形成的免疫复合物活跃。另一方面,未裂解的免疫球蛋白可抗原特异性和非抗原特异性地抑制免疫系统,而与F(ab')2或Fab抗体形成的免疫复合物则不然。有迹象表明,由于组织和白细胞蛋白酶的作用,这些裂解产物也会在体内出现。与Fab制剂不同,F(ab')2抗体具有与未裂解免疫球蛋白相似的抗菌和抗病毒效力,这可能是由于F(ab')2分子激活补体的能力,不是通过经典途径而是通过替代途径。与Fab制剂一样,F(ab')2分子在消除半抗原方面似乎优于未裂解的IgG。由于未裂解的免疫球蛋白在血液中停留的时间相对较长,它们非常适合长期的预防性治疗和替代治疗。主要从实验研究中获得的关于炎症介质释放减少、缺乏免疫抑制和IgG分解代谢增加的证据在多大程度上支持使用F(ab')2裂解产物,特别是用于治疗目的,只有在进行前瞻性和比较性研究之后才能确定。