RU2131746C1 - Method of immunocorrection of pathogen carrier - Google Patents

Abstract

FIELD: medicine, immunology. SUBSTANCE: lymphostimulating agents are administrated preliminary to pathogen carrier during blood extracorporal treatment and blood is separated for erythrocyte and plasma fractions. Erythrocytes are washed out and plasma is subjected for effect of immobilized proteins: cellular receptors of carrier that are complementary to pathogen, protein A, β- and i-chains of histocompatible protein of class-II and activating antigens. For work activating antigens, β- and i-chains of histocompatible protein of class-II are used being from the damaged organ of the carrier. If donor material is used then activating antigens, β- and i-chains of proteins that are identical or similar structurally with proteins of the pathogen strain by that the carrier is infected are used for work. Washed out erythrocytes and treated plasma are combined and administrated to patient. EFFECT: effective purification of pathogen carrier blood from the broad pattern of biologically active endo- and exogenic toxic substances. 9 cl, 1 ex

Description

 The invention relates to medicine and can be used in the treatment of carriers of bacterial, fungal or viral pathogens.

 The rapid development and widespread use of sorption methods for extracorporeal blood purification of patients in recent years is explained not only by their relative simplicity and accessibility, but also by new possibilities in the treatment of patients with severe illness.

 There is a method of extracorporeal immunocorrection of a pathogen carrier by washing the red blood cells of its blood from toxic biologically active compounds deposited on their surfaces (A.S. N 1811857, A 61 M 1/34, 1988).

 However, this known method allows you to clean only red blood cells.

 A known method of lymphostimulation (A.S. USSR N 1812995, A 61 M 1/34, 1987).

 However, this known method allows you to cleanse the body only of those toxic metabolites that circulate in the intercellular spaces.

 A known method of immunocorrection of a carrier of a pathogen, including extracorporeal treatment of his blood with an immobilized protein (US patent N 4681870, A 61 M 1/34, 1978).

 This known method allows you to clean the blood of the carrier of the pathogen from concomitant pathogenic flora and from non-specific antibodies.

 However, many pathogens can cause autoimmune processes in the carrier, as a result of which specific antibodies are formed, the purification of the blood from which is not promoted by the immobilization of the protein.

 A known method of immunocorrection of a carrier of a pathogen, including extracorporeal treatment of its blood by exposure to it with immobilized cellular receptors of a carrier complementary to the pathogen. As such sites in this known method for immunocorrection of HIV carriers, the CD 4 cell receptor was used (Biogen, Tnc // Appl Genet News - 1989, Vol 9 N 11 p. 4-5) [4] prototype.

 This known method allows you to cleanse the blood of pathogen proteins that can interact with cellular receptors, as well as from the corpuscular form of the pathogen. It also provides for the removal of antibodies from the blood, but only antibodies to this receptor.

 However, with a number of infectious diseases (viral hepatitis, measles, HIV infection), antibodies to the components of the histocompatibility protein of class II accumulate in the carrier’s blood, which cannot be removed from the blood using immobilized cell receptors used in this known method. In addition, this known method does not allow the blood to be purified from antibodies to activation antigens of immunocompetent cells, and these antibodies also accumulate in the patient's blood during the development of infection.

 The technical result achieved by the implementation of the present invention is the effective purification of the blood of the pathogen carrier from a wide range of biologically active toxic substances of endo- and exogenous nature.

 This is achieved by the fact that in the method of immunocorrection of the pathogen carrier, including extracorporeal treatment of its blood by exposure to it with immobilized cell receptors of the carrier complementary to the pathogen, a distinctive feature is that it is additionally affected by class II histocompatibility protein chains immobilized.

 In addition, they are affected by the histocompatibility class II protein i-chains.

 It is recommended to use the β and i chains of the organ of the carrier or donor that is affected by the pathogen in the carrier.

 When using donor material, those β and i chains that are structurally identical or similar to the proteins of the strain of the pathogen with which the patient is infected are taken into work.

 Additionally carry out the impact of activation antigens, as well as protein A.

 The listed effects can be combined.

 Before extracorporeal blood treatment, a lymphostimulant is administered to the carrier, blood is extracorporeally differentiated into the erythrocyte fraction and plasma, the erythrocyte fraction is washed, the plasma is treated with the listed means, and then the washed red blood cell and treated plasma fractions are again combined.

 Unlike prototypes, the method according to the invention used extracorporeal blood treatment with immobilized β- and i-chains of the protein of the main histocompatibility complex of class II, which allows removing antibodies to the components of the histocompatibility protein of class II from the blood of the pathogen carrier.

 By the method according to the invention, in contrast to the prototype, extracorporeal blood treatment with immobilized activation antigens was first used.

 In contrast to the prototype, blood treatment was applied with precisely those immobilized β- and i-chains of histocompatibility protein of class II, which are isolated from the material of the affected organ of the patient or the same organ of the donor. At the same time, it was recommended for the first time to use the β- and i-chains of the histocompatibility protein of class II only of the donor in which they are structurally identical or similar to the proteins of the strain to which the carrier is infected.

 For the first time, it is recommended to combine the effects of all known and newly recommended immobilized proteins.

 For the first time, extracorporeal blood purification is recommended to be preceded by the administration of lymphostimulants to the carrier, and the effect should be carried out only on the carrier's blood plasma; the erythrocyte fraction, having separated from the plasma, is washed and re-combined with the treated plasma.

 The following are examples of the implementation of the method according to the invention.

Example 1. Three HIV-infected patients before extracorporeal blood purification performed lymphostimulation. To do this, they were alternately given intravenously hemodez, reopoliglyukin, acesol, euphilin, proserin, heparin and calcium gluconate, after which they started extracorporeal purification of their blood. First of all, in a centrifuge, blood was extracorporeally divided into a erythrocyte fraction and plasma. The red blood cells were washed, and the plasma was subjected to alternating exposure to immobilized proteins:
- cellular receptors complementary to the pathogen, a commercial preparation of the CD4 protein;
- β-chains of histocompatibility protein of class II;
- Class II histocompatibility protein i-chains;
- activation antigen (CD26).

 In patients A., K., and M., the skin, forearms, chest, and larynx of the larynx were affected by Kaposi’s sarcoma, respectively. Accordingly, the necessary proteins were selected from patients from the materials of these organs.

 So in patients A. and M., proteins were taken from their own material of the skin and mucous membrane of the larynx. To clean the blood of patient K. infected with HIV-1, proteins obtained from a donor material (skin tissue sample) were used, in which the proteins of the four β-chains of histocompatibility class II, as well as the activation antigen CD26, had the same molecular weight as the surface glycoprotein dr 120, HIV-1, equal to 120 KD, and the i-chain, like surface glycoprotein dr 41, β-molecular weight 41 KD.

 Washed red blood cells and treated plasma were combined and injected into patients.

 The determination of viral RNA copies in blood plasma showed that the number of viral particles in 1 ml of carrier blood reached 1 million / ml before purification, and after purification it decreased by an average of 250 times. The number of T-helpers increased from 200-220 units / μl to 400-420 units / μl. As a result of the treatment, the level of serum IgG decreased by a factor of 2, and the number of causative agents of infections in the blood decreased by a factor of 3. After treatment, antibodies to histocompatibility proteins of class II and activation antigens were not observed in the blood.

 After the treatment, there was a decrease in the number and size of plaques of Kalosha sarcoma in patients A. and K., as well as partial healing of skin lesions in patient M. In all patients, the level of serum IgG, anti-lymphocytic AT, and serum inhibitory factors decreased. The determination of viral RNA copies in blood plasma showed that the number of viral particles in 1 ml of carrier blood reached 1 million / ml before purification, and after purification it decreased by an average of 250 times. The number of T-helpers increased from 200-220 units / μl to 400-420 units / μl. As a result of the treatment, the level of serum immunoglobulin decreased 1.5-2 times, the number of opportunistic infections pathogens decreased 2-3 times in the blood. After treatment, antibodies to histocompatibility class II proteins and activation antigens were not observed in the blood.

 The well-being of the patients improved markedly, all subjective sensations were removed.

 Processing was performed 2 times with an interval of 1 week. It is recommended to repeat the treatment monthly.

 Example 2. Patient D., 50 years old. He was admitted with a diagnosis of viral hepatitis. The preicteric period lasted 6 days. Upon receipt, a moderate condition. The tongue is coated in white. Marked yellowness of the skin and sclera. The liver is enlarged by 4 cm, compacted, painful. The spleen is not enlarged. Saturated urine, stool discolored. Total bilirubin 95.7 μmol / l, AlAT 1590 nmol / s. l , thymol sample - 8.0 Er - 4.8 • 105120 / l; L - 5.3 • 10590 / l, VOE 11 mm / h. HBsAg detected in serum. Clinical diagnosis: moderate hepatitis. As a result of immunocorrection, the appetite was restored, intoxication disappeared, bilirubin decreased to 27.0 mmol / l, AlAT 727 nmol / s. The release of HBsAg ceased. The activity of AlAT was normalized in the future to 88 nmol / sl (by the 30th day). The term of treatment in the hospital is 17 days. Remission lasts more than 5 months.

 Example 3. Patient K., 47 years old. Diagnosis: chronic cholestatic hepatitis. At admission, the patient complained of itchy skin, weakness, jaundice, joint pain. Sick for 5 years. Repeatedly treated in hospitals without a visible effect. Objectively, the patient's condition is satisfactory, the skin is sharply icteric, traces of scratching are noticeable, xanthomas and xanthelasms are determined. The abdomen is slightly swollen, the liver is dense, increased by 7 cm. The bilirubin content in the blood is 88 mmol / L, mainly due to the direct fraction, cholesterol 8.2 μmol / L, protein 82 g / L, gamma globulin 23%, AlAT 3 activity , 21 mmol / L, sublimate titer 1.4 U / L, thymol sample 130 units, the percentage of aggregated red blood cells 74.75%. The total volume of perfused blood is 9 l, the interval between blood processing is 7 days.

 After treatment, the patient’s condition improved significantly, weakness, jaundice decreased, skin itching disappeared, the state of the protein was 83 g / l, gamma globulin 21%, bilirubin became 21.3 μm / l, cholesterol 6.3 μmol / l, AlAT activity 0, 70 mmol / l, Sulimoproba 1.85 U / L, thymol sample 60 units, the percentage of aggregated red blood cells 45. The duration of treatment in a hospital is 40 days. Remission lasts more than 11 months.

Claims (9)

 1. A method for immunocorrection of a pathogen carrier, including extracorporeal treatment of its blood by exposure to it with immobilized cell receptors of a carrier complementary to the pathogen, characterized in that it additionally acts on the blood with immobilized β-chains of class II histocompatibility protein.  2. The method according to p. 1, characterized in that the blood is additionally affected by immobilized i-chains of class II histocompatibility protein.  3. The method according to claim 1, characterized in that they effect the immobilized β and i chains isolated from the organ that is affected by the pathogen.  4. The method according to claim 1, characterized in that they effect the immobilized β and i chains isolated from the donor material, structurally identical or similar to the proteins of that strain of the pathogen with which the carrier is infected.  5. The method according to claim 1, characterized in that it additionally acts on the blood with immobilized activation antigens of the affected organ.  6. The method according to claim 1, characterized in that it additionally affects the blood with immobilized protein A.  7. The method according to claim 1, characterized in that the blood is exposed to immobilized histocompatibility protein i-chains of class II and / or immobilized β and i-chains isolated from the organ that is affected by the pathogen and / or β and i -chains isolated from donor material, structurally identical or similar to the proteins of the strain to which the carrier is infected, and / or immobilized activation antigens of the affected organ and / or immobilized protein A.  8. The method according to claim 1, characterized in that before extracorporeal blood treatment, lymphostimulants are administered to the carrier.  9. The method according to claim 1, characterized in that before exposure to the carrier blood with immobilized proteins, it is extracorporeally differentiated into the erythrocyte fraction and plasma, the erythrocyte is washed, the indicated effect is applied to the plasma, and then the washed erythrocyte fraction is again combined with the plasma subjected to the indicated effect.