JPH05508220A - Methods for the detection and preparation of anti-IgE autoantibodies and the use of these antibodies as active agents in diagnostic and therapeutic compositions - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Methods for detecting and preparing anti-IgE autoantibodies and these two products that have sold out Use as an activator in The present invention provides a method for detecting anti-IgE autoantibodies in body fluids, a method for preparing autologous anti-IgE antibodies, and and the use of these antibodies for diagnostic and therapeutic purposes.

The existence of antibodies directed against distinct immunoglobulin isotypes is widely documented in the literature. It is listed. For example, anti-IgE autoantibodies have been described as eumatoid factor and are associated with disease (Magnusson C, G, M, ), Vaerman J, P, Int, Arc h, Allergy appl, Immunol, 79 (1986) , 149, Stevens (W, J, ), Blibb (B ridts C, H,), J.

Allergy clin, I mmunoll, 73 (1984), 276 , Iganas M, J ohansson S, G, O,), Bennich H, Int, Ar chs, Allergy Appl, Ia+muno1.65 (1981), 51).

Anti-IgE autoantibodies were first described in 1972 (Will ia+msR,C,), Griffith R,W,), Emmons (E+s+aons J, D,), Field (Field R, C,), J, C11n, Invest: 5H1972), 955-1003). After that, Specific anti-IgE autoantibodies such as Ta (Nawata Y,), Koike (T,), Hosokawa (Hosokawa) kavaH,), Tomoika H,), Yoshida S.), J. Immunol, 135 (1985), 478; Nawata, Ko. Iga, Yanagisawa T, Iwamot o1. ), Itaya (I taya T, ), Yoshida, Tomioka (Tomio ka H,), C11n.

Exp, Imm+uno1.58 (1984), 348;:+Ike, Nawata, Tsutsumi (Tsutsu+miA,), Tomoika, Allergy Today 2 (1987), 4: and Gruber (B, L.), Baeza (B. aeza M, L,), Marchese (M, J,), Agnello V, Kaplan A, P, ), J, Invest, Der+*ato1.90 (1988), 2 13), and also in association with non-atopic diseases with elevated serum 1gE levels (status S tadler B, M, Nakajima K,), Young (YangX,), De Week A, L,), Int, Arch, Allergy Appl, Immun ol, 88 (1989) 206-208). However, high Bell's anti-1gE autoantibodies have also been found in normal individuals (Stadler, N. Kajima, Young, Dounitsuku, Tnt, Arch, Allergy Appl, Immunol, 8g (1989); 206-208, U Wilson P, B, Fairfield d J, E,), Beach (Beech N,), Int, Archs, Al lergy Appl, I mmunol.

84 (1987) 198).

In in vitro experiments, human basophils, tissue mast cells and passively sensitized Anti-IgE autoantibodies can trigger the release of histamine from human bone marrow cells. Shown (Marone G, ), Cabra o (Casolar o V, ), Paganel! Paganelli R.), Quint. i1. ), J, I nvest, Dermatol, 93 (1 989) 246-252; Kinch, Brozek (C,), Wood (Wood N,), Geha R, S, Leung D , Y, M, ), J, Allergy C11n, I mll1unol .

77 (1986), 586-594). However, in other cases IgE autoantibodies can cause histamine release from blood basophils. There was none (Nakajima, Dou Unitsuk, Stadler, Allergy 44 ( 1989), 187-191; Kemeny:--(Kemeny D, M,), Tomoika, Tsumi, Koiga, Lessof (M, H,), Lee (Le e T, H,), C11n, Expert, Allergy 20 (1990), 67-69; Devey M, E, Wilson, Wheeler (Wheeler A, W.), C11n, Allergy 6 (1976), 2 27-236). Pathophysiological role of anti-1gE autoantibodies in allergic diseases , the methods used to detect them, such as ultracentrifugation. The essential reason is that it is technically difficult and unsuitable for large-scale research. , has not yet been elucidated. Therefore, in humans, anti-IgE autoantibody The literature still does not provide a clear picture of the harmful or possible beneficial role played by the body. has not emerged.

It is therefore an object of the present invention to provide a simple and reliable method for the quantitative detection of anti-IgE autoantibodies. The goal is to provide a method for

The object of the present invention is also to treat allergic diseases and other diseases in which anti-1gE autoantibodies are involved. Human anti-IgE autoantibody to evaluate the function of anti-IgE autoantibody in patients It is a method of identifying functional categories. Another object of the present invention is allergic diseases and anti-IgE useful in preparing therapeutic agents for other diseases involving IgE. This is a method to screen human plasma containing autoantibodies.

Another object of the present invention is to provide a method for purifying anti-IgE autoantibodies with specific properties. There is a particular thing.

Another object of the present invention is that by active immunization with selected recombinant IgE fragments, producing selected anti-IgE autoantibodies with desired properties in vivo; be.

The invention consists of subject matter as defined in the appended claims.

Autologous anti-IgE antibodies can be detected in free form or in the form of IgE-IgG complexes. can be done. Its fine specificity is achieved by using recombinant IgG fragments. can be positioned.

The invention is illustrated in the following drawings and the following examples (which relate to specific aspects of the invention) Please describe in more detail.

Figure 1a shows the principle of the direct assay for the detection of anti-IgE antibodies.

Figure 1b shows a sandwich assay for the detection of IgE/anti-IgE autoantibody immune complexes. Demonstrates the principle of the test.

Figure IC shows the principle of the competition assay for the determination of the specificity of anti-1gE autoantibodies. .

Figure 2 is a diagram corresponding to Table 4, showing the response to anti-IgE antibodies in Rh monkeys. Shows a sarcastic reaction.

Figure 3 is a diagram corresponding to Table 5, containing various amounts of anti-IgE antibodies. Various human sera from Le27 monoclonal antibody -4) to act on “stripped J” human basophils resensitized with The effect on histamine release induced by and.

Figure 4 shows that various sera containing various amounts of anti-IgE antibodies Diagram showing the effect of null antibody on Rhesus skin response to anti-IgE It's rum.

Figure 5 shows immunoadsorption consisting of various r　I　gE (CHI-4 or CH3-4). Human anti-IgE antibodies (pool) purified by passing over a Rhesu column Diagram showing effects on Le27-induced skin responses in S monkeys. It's rum.

Figure 6 shows human serum and anaerobic serum after treatment with allergen/IgG anti-allergen mixture. Preoperative serum and classically desensitized patient serum are FIG.

Figure 7 shows the serum of Rhesus immunized with rIgE, the serum before treatment, and the serum of Rhesus immunized with rIgE. The serum of Rhesus immunized with the allergen was induced by the allergen. This is a diagram showing the effect on histamine release.

Example 1 This is due to the presence of autologous anti-1gE antibodies and the microscopic presence in the direct assay (Fig. 1a). Purified 1gE myeloma, chimeric IgE antibody, recombinant ■ to assess specificity gE fragments and/or IgE synthetic peptides and monoclonal anti-IgE antibodies by nitrocellulose-coated plastic strips using It's a test. This type of assay typically uses 100-1000 μg/ml. Depositing the IgE material onto the solid phase material in the form of 1-2 μm dots at a range of concentrations. .

After blocking the adjacent solid phase region with neutral proteins, the serum sample to be examined Coat the strip with trocellulose (diluted 1:10 to 141). (preferably made of glued PVC) is incubated for 1 to 18 hours. suitable After washing, the monoclonal cells were labeled with horseradish peroxidase (HRP). Anti-gE antibody (crosslinked with either IgE and/or dotted IgE material) (no reaction). IgG subclasses (e.g. I gG1.2.3.4) or other immunoglobulin classes (e.g. A, M) When using monoclonal antibodies against can be determined. This second incubation is usually 1-2 hours and Incubate with chromogen at In the case of HRP labeling, the preferred chromogen The body is a mixture of 2-4 chloronaphthol and hydrogen peroxide. The blue that appears after that Quantitatively measure the small dots using a suitable refractometer.

Examples of direct detection of IgG autoanti-1gE antibodies in various samples or plasma are shown in Table 1. This immunized the presence of autologous anti-1gE antibodies in a sandwich assay (Figure 1b). nitrates using various monoclonal anti-1gE antibodies to evaluate in the form of complexes. Cellulose/PVC strip test.

In this case, the dotted substances are specific for various epitopes on the IgE molecule. It is a well-defined monoclonal anti-IgE antibody. Serum to be investigated After incubation with the sample, free IgE and immune complexes ), HRP-labeled monoclonal anti-I A second incubation with gG G anti-1gE immune complexes will be detected. Temporal control and quantitative evaluation of reactions The value is essentially the same as in Example 1 above.

Detection of such IgG anti-IgE immune complexes in serum samples and plasma pools Examples are shown in Table 1.

Example 3 This was compared to IgE myeloma, IgE recombinant peptides in competition assays (Figure 1c). using anti-IgE monoclonal antibodies and anti-IgE monoclonal antibodies, either in free or complexed form. Nitrocellulose/PVC strip for detecting the fine specificity of anti-1gE antibodies This is a trip test.

In this method, first, IgE myeloma and/or recombinant IgE peptides are Dot the dot onto the solid phase. ink for 2 to 18 hours with the serum sample to be investigated. After rinsing and washing appropriately, the selected HRPIl [anti-1gE monoclonal Perform a second incubation with antibody. If the serum sample is labeled with the HRP If it contains an IgE antibody with the same epitope specificity as the anti-IgE antibody, the reaction will be suppressed. In this way, we currently have at least five different Epitopes have been identified on IgE molecules.

Examples of detection of autologous anti-1gE antibodies with various specificities in human serum are shown in Table 2. . This method may be associated with some specific IgE functions, Identification of specificity patterns that may form the basis for the selection of immunoglobulin preparations It is what makes it possible. Through such identification procedures, suppressive effects on allergic diseases can be achieved. It becomes possible to prepare certain anti-allergic human autologous anti-1gE antibodies.

In addition to immunochemical detection and determination of fine specificity by the techniques described above, autoantibody E antibodies may also contain histamine and/or sulfur from, for example, blood basophils. Release of sulfidoleukotrienes, I Effect on binding of gE to lymphocytes, lethality to B lymphocytes with IgE can also be investigated by functional assays such as effects on IgE synthesis. Wear.

By doing so, autologous anti-IgE antibodies have a wide range of different functional properties. and that these functions have fine specificity, avidity, and perhaps found to be associated with a class or subclass of autologous anti-1gE antibodies . By combining these various assays, in fact some self-extracting g E antibodies play important pathological roles, and other antibodies exhibit opposing and advantageous functions. There was found.

The above immunochemical assays can be used for various treatments and corresponding treatments, as explained below. Provides a rational and effective platform for the development of therapeutic products.

Prepare anti-allergic immunoglobulin preparations according to the content of autologous anti-1gE antibodies. Appropriate plasma can be selected that is suitable for use. In such a procedure, Plasma obtained by blood transfusion or plasma exchange method is freed by the above immunochemical test. Or screen for the content of anti-IgE antibodies as a complex. in plasma According to the content of such antibodies and their specificity, the plasma was pooled and subjected to several mechanisms. The functional properties (eg histamine release) are also tested. The selected plasma was Then, classical methods in the art (e.g., alcohol fractionation or ion fractionation) are used. Processed to prepare immunoglobulin fractions by exchange chromatography) do.

Example 4 Human plasma obtained by plasmapheresis separation method was treated with anti-1gE antibody (Table 3) and/or and immunodot tests for the detection of sulfide leukotrienes. this plasma was also examined for its ability to induce histamine release from human basophils ( Table 3). Contains no, low levels, or high levels of anti-1gE antibodies. pooling the plasma having no histamine-releasing capacity or having a high histamine-releasing capacity; Immunoglobulin fractions are prepared by ion exchange chromatography.

When tested in Rhesus monkeys by sarcastic injection (Table 4 and corresponding Fig. 2), Human immunoglobulin preparations lacking autologous anti-gE antibodies cause allergic reactions I know that it doesn't. In contrast, autoantigens of the anaphylactic nature gE antibodies cause allergic reactions (Table 4). cause anaphylaxis Some sera contain anti-IgE antibodies that do not cause anaphylaxis or anaphylaxis. was induced in Rhesus monkeys by the mouse monoclonal anti-1gE antibody Le27. It is possible to suppress the skin reaction that occurs (Figure 4).

When used on blood basophils in histamine release assays, anaf Lacking anti-IgE antibodies that cause iraxis (some serum or Igm products are will inhibit the effect of anti-Ig'E antibodies that cause anaphylaxis (Table 5 and corresponding Fig. 3). A similar inhibitory effect of Ig preparations may produce anaphylaxis. Immediate wheal and erythematous skin induced by anti-1gE antibodies Reactions can also be observed, thereby indicating its therapeutic potential.

Sheep anti-1gE antibodies directed against human IgE also target IgE receptors. It also has the property of killing expressing IgE-containing cells (CD 23). Similarly, some human anti-IgE antibodies have similar potential in vitro, thereby possibly It is likely that it will exhibit an inhibitory effect on IgE synthesis in vivo.

The desired therapeutic properties of some anti-IgE antibodies are, as mentioned above, due to their fine specificity. (Assessed by interaction with IgE recombinant fragment and anti-IgE monoclonal antibody) can be used), using relevant IgE recombinant fragments. Passing the selected plasma through the prepared affinity chromatography column attempts to obtain purified immunoglobulin preparations with the desired anti-IgE specificity. saw.

Example 5 Plasma containing anti-IgE antibodies selected by the above immunodot test was treated with recombinant IgE antibodies. Pass through a chromatography column prepared using the gE fragment. Next, prepare 1g The material is processed according to methods well known in the art.

Such a 1 g preparation was shown to be effective in functional tests in humans and monkeys (Figure 5). , exhibiting desirable protective properties in preventing allergic reactions. Indeed, selected plasma fractions Purified autoantibody 1 obtained by separation exchange method and passed through a suitable IgE recombinant peptide column. Preparations of gE antibodies are made from whites of allergic patients challenged with allergen or anti-IgE. It can suppress histamine release from blood cells. It can also be acid treated and assembled. Anti-1gE monoclonal that reloads with modified IgE fragments and causes anaphylaxis Humans are made of white blood cells that are first "stripped" of their own IgE by attacking them with antibodies. Stamine release can also be inhibited (Table 5). It's a mouse monoclonal Skin reaction induced by anti-IgE Le27 antibody in Rhesus monkeys can be suppressed (Figure 5).

Classically, these include those that occur naturally in some patients with severe allergies, or desensitization. such as those caused by repeated injections of allergens during therapy. Allergen-specific IgG antibodies are advantageous and function as inhibitory antibodies in vivo. (Doubay, Wilson, Wheeler, C11n, Alle rgy 6 (1976), 227-236; ), Malling (HJ, ), Sondergaard (S oen dergaard I,), Weeke B,), J, A1-) ergy C11n, I++uauno1. ．． 76 (1985), 46-5 5). However, the beneficial role of such antibodies is under debate. and the level of 1gG anti-allergen antibodies reached during desensitization therapy and its treatment clinically. It must be emphasized that there is little correlation between No (Golder + D.

B, Ni,), Meyers (D, A,), Caggy-Sobotka ( Kagey-S robotkaA, ), Valentine M , D, ), Liechtenstein (L1chtenstein L.

M, ), J, Allergy clin, I mmunol, 69 (1 982), 489-493).

This led some authors to consider other methods, namely the use of anti-idiotypic immunization. I decided to try (Saint-Remy J, M, R,), Lebecque S, J,), Lebru n　P,　M,　), Jackman (J　acquen+in　M,　G,　) , Eur, J., Immunol, 18 (1988), 1009-1014 ), which causes the patient to produce anti-allergen IgG antibodies and makes such antibodies purification on an affinity chromatography column and then in vitro. It consists of reinjecting the patient with his own antibodies complexed with the allergen ( US-A-4740371). This method is applicable to various categories suffering from IgE-related diseases. It is said to offer clinical advantages to patients with Leigh allergy.

In fact, surprisingly, allergen affinity chromatography columns The majority of apparently allergen-specific IgG antibodies isolated by the It is not an allergen-specific IgG as previously believed, but an IgG autoanti-I It turned out to be allergen-specific IgE bound to gH.

In other words, IgG anti-IgE and complexed with allergen-specific IgE Immunization with allergens and allergens induces beneficial immunological changes associated with immunotherapy. Caused in allergic patients. As mentioned above, the mechanism of IgG autoanti-IgE The therapeutic effects are very different according to their minute specificity, so these treatments are Evaluation with anti-IgE antibodies is inevitable.

Plasma from hypersensitized patients was collected based on the apparent IgG specificity for the allergen. Allergens (e.g. grass pollen) Select based on specific 1gG test and analyze for presence of autologous anti-IgE antibodies .

Plasma pools rich in autologous anti-IgE antibodies or lacking autologous anti-1gE antibodies are subjected to immunoglobulin used as a source of bulin preparation, which is then complexed with the allergen and applied to the skin. Inject meat. In such cases, allergen-specific IgG in the plasma pool and increased Preparation of a complex between a given amount of allergen and the patient's susceptibility to the corresponding allergen according to an empirical schedule based on gender. Field of grass pollen mixture Table 7 shows the preferred schedule for this case. The effect in allergy patients is ironic Assessed by provocation and histamine release (Figure 6). As you can see from this diagram, The effect of such treatment is to reduce the reactivity of the patient and the reactivity of the cells to the allergen. The aim is to produce antibodies that reduce

In principle, this technique is based on IgE, such as immune defense against certain parasites. It can also be used to promote other active immune responses. IgE The presence of inhibitory antibodies against, for example, filialosis )It is described in.

Therefore, in order to produce advantageous anti-IgE antibodies in allergic patients (I gE-Vaccine) Active immunization with IgE recombinant fragments becomes possible.

As mentioned above, several naturally occurring anti-IgE antibodies are useful for allergic patients. advantageous, and that this advantage is due to the fine-grained Epitopes associated with favorable anti-IgE responses have been found to be associated with specificity. Similar anti-1gE antibodies can be generated by immunizing with the appropriate IgE fragment containing only the Attempts can be made to actively produce it.

Therefore, IgE complexed with allergen, recombinant IgE, or recombinant IgE fragments prepared surgically and selected for favorable anti-IgE association are immunized with and inject it into experimental animals. Desired suppressive anti-allergic effect Anti-IgE antibodies of desired specificity can be actively prepared.

Example 7 Recombinant IgE peptides of different sizes encompassing different domains of the IgE heavy chain were Manufactured using a combination of methods known in the art.

These fragments are further analyzed by affinity chromatography columns. Immunodot assay for detection of autologous anti-IgE antibodies, as in body purification Once established, it can also be used for diagnostic purposes.

In a third application described herein, the selected domain CHI, -4 Selected fragments containing .

As shown in Table 6, the antibodies produced were similar to naturally occurring human autologous anti-IgE antibodies. Possesses the necessary functional properties based on previous analysis of the body. Toriwa However, these antibodies can recognize IgE and IgE fragments. These antibodies may also contain anti-IgE monoclonal antibodies or allergens that cause anaphylaxis. It has the ability to suppress the histamine release induced by ion (Figure 7).

Secondary effects when immunizing with recombinant IgE peptides that have not been completely purified The effect is to increase the natural levels of IgG antibodies against E. coli. this child Although this is not in itself undesirable, a more purified rIgE vaccine This can be avoided by using "

Table 2: Analysis of fine IgE epitope specificity by competition assay Containing autologous anti-1gE antibodies with different single or mixed specificities Table 4: Anti-1gE antibodies Cynic reaction of Rh monkeys to E antibody Monoclonal antibody anti-IgE By acting on "deprived" human basophils resensitized with E(CHI-4), Effect on induced histamine release Histamine release (%) by each addition Table 7: As maintenance dose every two weeks Allergen for use as a complex for the desensitizer method to last for one year and antibody schedule and amount.

Concentrated antibody* (mcg) Allergen (ng) 0 0.02-0.06 4- 16 2 0.04~0.16 8~32 4 0.08~0.32 16~646 0.16~0.64 32~128 8 0.32-1.28 64-25610 0.64-2.56 128-5 1212 1.28-5.12 256-1024 This schedule is for reference only. This is only an example, and may be changed depending on the strength of the antibody and allergen. principles and to neutralize sensitized basophils for in vitro allergen challenge, and To prevent mediator release under such conditions, sufficient antibodies are injected into the allergen. must be added to.

The antibody used is an allergen-specific rIgG antibody, which is an IgG anti-IgE antibody. It also contains anti-allergen IgE complexed with autoantibodies.

Anti-IgE autoantibody detection assay a) Direct assay b) Immunoconjugate sandwich assay - C) Competition assay FIG.3 FIG. 5 abstract In a method for detecting free or complexed anti-IgE autoantibodies, a sample, IgE peptides or recombinant IgE fragments bound to a solid support and incubated with an IgE substance in the form of . This method is a direct assay and can be performed as a sandwich assay or as a competitive assay. Ru.

This method is an anti-allergic human anti-inflammatory drug that has a therapeutic inhibitory effect on allergic diseases. Useful in methods of preparing 1gE antibodies. In this method, a predetermined amount of Human body fluids containing 1gE autoantibodies are selected according to the above method, preferably alcohol Immunoglobulins in the body fluids can be isolated by fractionation or ion-exchange chromatography. Concentrate. To obtain pure anti-rgE autoantibodies, the antibodies were extracted from the concentrated product. Isolate by affinity chromatography.

Anti-IgE antibodies and their complexes are useful in pharmaceutical compositions for the treatment of allergic diseases. Useful as an active ingredient.

Generation of autologous anti-1gE antibodies can be induced by IgE peptides or recombinant IgB fragments. Can be induced in vivo.

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Claims (17)

[Claims] 1. IgE substances in the form of IgE peptides or recombinant IgE fragments are linked to solid supports. The sample is brought into contact with the IgE substance on the treatment carrier and incubated. Free or complexed anti-IgE autoantibodies in biological samples characterized Detection method. 2. IgE peptides or recombinant IgE fragments can be covalently or electrostatically attached to a solid support. 2. The method of claim 1, wherein the method is coupled to. 3. A plastic sheet coated with nitrocellulose is used as a solid carrier. A solution containing 10 to 100 μg/ml of IgE substance is applied to the sheet in a line or 3. The method according to claim 1, wherein the test is carried out directly by depositing as a point. 4. When the deposition and binding of the IgE material is complete, neutral proteins release the carrier. 4. A method according to any one of claims 1 to 3, wherein the method is blocking. 5. For the sandwich test, the following steps: specific for the epitope of a given IgE molecule depositing well-defined monoclonal antibodies on a solid support, to the treatment carrier to capture free or complexed IgE substances from the sample. bringing the sample into contact; Quantitatively evaluate the anti-IgE autoantibodies in the sample as IgE/IgG anti-IgE complexes. Contacting the obtained carrier with labeled monoclonal anti-IgG in order to The method according to item 1 or 2. 6. In competitive tests, the IgE substance is bound to a solid support, and the washed support is It is incubated with the sample and then reacts competitively with the anti-IgE antibody in the sample. performing a second incubation with a labeled monoclonal anti-IgE antibody, The method according to claim 1 or 2. 7. The labeled monoclonal antibody is conjugated to an enzyme, such as horseradish peroxidase ( 7. The method according to claim 5 or 6, wherein the method is labeled with HRP). 8. A body fluid having a predetermined amount of anti-IgE autoantibodies according to any one of claims 1 to 7 selected according to the method, characterized by increasing the immunoglobulin concentration in the body fluid. Anti-allergic, anti-IgE anti-allergy that has a therapeutic suppressive effect on allergic diseases. How to prepare the body. 9. Anti-IgE antibodies by challenge with IgE peptides or recombinant IgE fragments 9. The method of claim 8, wherein the body fluid is obtained from an individual who has been induced in vivo. 10. Immunoglobulins are analyzed by alcohol fractionation or ion-exchange chromatography. 9. The method according to claim 8, wherein the concentration of ion is increased. 11. Request for isolation of anti-IgE autoantibodies by affinity chromatography The method according to any one of claims 8 to 10. 12. The anti-IgE autoantibody-containing mixture is preferably subjected to affinity chromatography. Recombinant IgE fragments or monoclonal anti-Ig Affinity chromatography by contacting a carrier bound with E antibody 12. The method according to claim 11. 13. IgE material in the form of IgE peptides or recombinant IgE fragments on a solid support and incubating the resulting carrier-bound IgE substance by bringing it into contact with a body fluid, Then, an anti-IgE antibody characterized by increasing the immunoglobulin concentration in the body fluid. By using a body detection method, human body fluids containing a predetermined amount of anti-IgE autoantibodies are detected. An anti-IgE autoantibody prepared according to a method characterized in that it selects. 14. In vitro with free form or allergen-specific IgG and allergens Claim 13 as a therapeutic agent for allergic patients in the form of a complex formed with anti-IgG autoantibodies. 15. Anti-IgE autoantibodies free or complexed with allergens and pharmacology Prevention or treatment of allergies characterized by comprising a chemically acceptable vehicle. Pharmaceutical composition for medical treatment. 16. When present, active immunization can produce appropriate autologous anti-IgE antibodies. recombinant IgE peptides, free or complexed with anti-IgE autoantibodies. Preventing allergy characterized by containing in a pharmacologically acceptable vehicle Vaccine compositions for preventive or therapeutic treatment. 17. Free or anti-IgE antibody according to claims 13 and 14 and allergen complex. A pharmaceutical composition comprising a recombinant IgE peptide that has formed a conjugate.