Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL (a) (Lp[a]) from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.
Sheep polyclonal antibodies to human lipoprotein(a) were used for the development of sandwich enzyme immunoassay. These antibodies virtually do not interact with human plasminogen, apoB-100, or fibrinogen in this assay. The method permits measurements of lipoprotein(a) in a wide range of concentrations: from 2 to 500 mg/dl. The variability of analyses within the range of 5 to 180 mg/dl is approximately 4.5% in a plate and 10.5% in different tests. Correlation analysis of the results of the enzyme immunoassay modification developed in our laboratory and of its foreign analogs showed a high similarity of the methods, the correlation coefficient being 95%.Lipoprotein(a), or Lp(a), is a lipoprotein particle containing a protein apo(a) unique to the lipoprotein family; it is bound to molecule apoB-100 with a covalent disulfide bond, and this molecule is the principal protein component of a corpuscle of low-density lipoprotein (LDL). Lp(a) was discovered by Berg in 1963 as a new antigen of human plasma and as a variant of LDL corpuscles [2]. Further studies showed that Lp(a) differs from LDL not only in composition, molecular weight, and electrophoretic mobility, but also in physiological role and metabolism [12].Active studies of Lp(a) were started after it was shown to be associated with the risk of atherosclerotic involvement of the heart [4], Further investigations clearly demonstrated that a high level of Lp(a) in the blood is closely related to the appearance and development of atherosclerotic lesions in various arteries [7,12].
Low density lipoprotein (LDL) (1,03-1,05 g/ml) was utilized as antigen to obtain polyclonal (PcAb) and monoclonal (McAb) antibodies. Immunosorbents capable of selective removing LDL from human plasma were developed on the basis of the antibodies preparation. The sorbents called "Immunoliposorber PcAb" and "Immunoliposorber McAb" are currently undergoing clinical trials in the USSR Cardiology Research Center, Acad. of Med. Sciences.
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