RU2139100C1 - Method of treatment of patients with allergic diseases - Google Patents

Abstract

FIELD: medicine, allergology. SUBSTANCE: method involves plasmaphoresis and successive heating each sample of patient plasma up to 56 C followed by its recovery to patient but without a precipitate. Number of procedures is decreased up to the native IgE level 100 ng/ml. Treatment effect is based on the heating to 56 C when capability of IgE to bind with mast cells is lost as a result of conformation alternations of Fc-fragment of an immunoglobuline molecule. EFFECT: enhanced effectiveness of treatment of allergic diseases. 1 cl, 1 ex

Description

 The invention relates to medicine, namely to efferent methods for the treatment of allergic diseases.

 The main link in the pathogenesis of allergic diseases proceeding as an immediate hypersensitivity is the presence of circulating and in the tissues immunoglobulins E (IgE), which, after binding to the antigen, are sorbed on the surface of mast cells, leading to degranulation of the latter and the development of a pronounced inflammatory reaction (Clinical Immunology. // Under the editorship of L. Yeager. M: Medicine, 1986, v. 2, pp. 20-150.). Therefore, the treatment of such conditions consists of effects aimed at suppressing inflammation: anti-inflammatory drugs, agents that stabilize mast cell membranes, antihistamines and plasmapheresis, as a way to reduce the amount of circulating IgE. (Handbook of a practical doctor. // M.: Medicine, 1988, v. 1, pp. 60-68). In addition, specific immunosorption is used, which consists in the use of specific anti-IgE antibodies sorbed on a solid carrier during the plasma adsorption session, eliminating reagins from the bloodstream. (Immunocorrection in pulmonology. M: Medicine 1989, p. 202-210).

 A known method of drug therapy, which consists in the use of anti-inflammatory drugs (aspirin, ibuprofen, voltaren, hydrocortisone), means for stabilizing mast cell membranes (cromolyn sodium), antihistamines (diphenhydramine, pipolfen). (Handbook of a practical doctor. // M .: Medicine, 1988, v. 1. S. 60-68).

 The disadvantage is the symptomatic nature of drug therapy, an insufficient decrease in the level of immunoglobulin E, both free and contained in circulating immune complexes.

 The closest way to the claimed is a method of treating allergic diseases, based on immunocorrection using specific immunosorption of IgE. (Immunocorrection in pulmonology. M .: Medicine, 1989, p. 202-210), which consists in the use of specific anti-IgE antibodies adsorbed on a solid carrier eliminating reagins (IgE) from the bloodstream during a plasma adsorption session. The disadvantages of this method of treatment are the complexity, low capacity and instability of the used immunosorbents (heteroantibodies to IgE).

 The objective of the present invention is to increase the effectiveness of the treatment of allergic diseases associated with the presence of immunoglobulins E.

The task is achieved by the fact that with plasmapheresis, each portion of the plasma taken from the patient is sequentially heated to 56 ^° C, followed by its return without sediment to the patient, while the number of procedures is performed until the level of native IgE is reduced to 100 ng / ml.

The treatment effect is achieved due to the fact that when heated to 56 ^o C, IgE loses its ability to bind to mast cells due to conformational changes in the Fc fragment of the immunoglobulin molecule (Clinical Immunology. // Under the editorship of L. Yeager. M .: Medicine, 1986 , v. 2, p. 27). Thus, by heating a sufficiently large volume of plasma, almost the entire amount of circulating IgE can be converted, which will lead to a weakening of the allergic reaction due to the binding of the allergen to heat-treated IgE, which will not cause mast cell activation. The described method of treatment, in comparison with the analogue, allows to achieve a more stable remission of the patient's condition, and to reduce the duration of treatment during exacerbation of the disease.

 The essence of the method is as follows.

 Treatment is carried out for patients with nosology, which are based on immediate hypersensitivity (excluding anaphylaxis), during an exacerbation of the symptoms of the disease and in the presence of an amount of IgE in the bloodstream exceeding 100 ng / ml, without concomitant acute or chronic bacterial infections, against the background of basic drug with or without therapy, a series of plasma thermal modification sessions is carried out until normalization (less than 100 ng / ml) of the number of native circulating IgE (determined by the enzyme immunoassay using mon Clonal antibodies to the Fc fragment of the test reagents). Before each session, complement activity and the amount of fibrinogen are monitored. If the activity of the complement system (in units of CH 50) is reduced to 30 (lower limit of normal) or the fibrinogen content in peripheral blood is less than 4 g / l (lower limit of normal), then the next session is transferred until the increase in complement activity above 30 Units CH 50, or fibrinogen level above 4 g / l.

The thermal modification procedure is carried out using the apparatus for plasmapheresis PF50 using heparin 3000 - 10000 I / O. Plasma is taken in several doses into 450 ml vials so as to process as much of the patient's plasma as possible. Each vial is heated in a water bath at a temperature of 56 ^o C for 15 minutes (enough time to warm the entire vial to the required temperature), then centrifuged for 10 minutes at 1000g, the supernatant is transferred to a clean sterile vial, which they return to the patient with treated plasma.

 Example: Patient Ivanov I.I., 30 l. He was admitted to the hospital with a diagnosis of allergic bronchial asthma, a state of asthmatic status.

When conducting laboratory tests found:
The number of detected circulating IgE - 2000 ng / ml,
Complement activity - 70 units of CH 50
The amount of fibrinogen - 6 g / l
It was decided to carry out a plasma thermal modification procedure. A thermoplasma treatment session was carried out using a PF50 plasmapheresis apparatus using heparin 5000 U / V. Plasma was taken in four doses in 450 ml vials, i.e., for the entire treatment session, the volume of treated plasma was 1.8 liters. Each vial was heated in a water bath at a temperature of 56 ^o C for 15 minutes, then centrifuged for 10 minutes, the supernatant was transferred to a clean sterile vial, from which the treated plasma was returned to the patient.

After treatment, the patient left the state of asthmatic status. The next day, the laboratory indicators were as follows:
The number of detected circulating IgE - 1000 ng / ml,
Complement activity - 60 Units CH 50,
The amount of fibrinogen is 5.4 g / l.

 It was decided to conduct another procedure for thermal modification of the plasma as described above. After the procedure, the patient's condition is satisfactory.

Laboratory indicators the next day:
The number of detected circulating IgE - 200 ng / ml,
Complement activity - 50 units of CH 50,
The amount of fibrinogen is 4.7 g / l.

 Given that the amount of IgE has decreased, it was not decided to conduct another procedure for thermal modification of plasma. After a treatment session, the patient's condition is stable. The number of detected IgE in the peripheral blood after a thermoplasma modification session is 20 ng / ml. Further use of thermoplasma treatment is considered inappropriate, since the level of IgE is reduced sufficiently.

 After 7 days, the patient was discharged in satisfactory condition.

 After treatment, the patient had no asthmatic attacks for 4 months.

 The method of thermal modification has been clinically applied at the State Scientific and Clinical Center for Miners' Health, 34 patients were treated, all patients noted an increase in the period of remission, and the absence of side effects of therapy.

Claims (1)

A method of treating allergic diseases associated with immediate hypersensitivity, based on the use of immunocorrection, characterized in that during plasmapheresis, each portion of the plasma taken from the patient is sequentially heated to 56 ^° C, followed by its return without sediment to the patient, while the number of procedures is carried out until reduction native IgE levels up to 100 ng / ml.