Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes.

Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double-blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side-effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization.

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. V. Auto-anti-idiotypic antibody characterization and cross-reactivity.

From the serum of 10 allergic subjects we have prepared IgG antibodies recognizing idiotopes carried by specific antibodies to Dermatophagoides pteronyssinus (Dpt) allergens, and studied cross-reactivity of anti-Dpt IgG bystander and antigen-binding site-associated idiotopes by latex agglutination assays. Idiotopes of specific anti-Dpt IgE were evaluated by radioimmunoassays. Depending on the assay, a binding or inhibition of more than 50%, as compared to the reactivity of specific antibodies with the corresponding anti-idiotypic (anti-Id) IgG, was considered significant. Cross-reactivity of antigen-binding site-associated idiotopes attained a mean proportion of 6/10 for IgG and 9.6/10 for IgE. By contrast, bystander idiotopes cross-reacted only occasionally with a mean proportion of 2/10 for both IgG and IgE antibodies. Anti-Id antibodies from two subjects have been isolated by adsorption on insolubilized anti-Dpt antibodies of the corresponding patient. Using this purified material we have confirmed that (a) the majority of anti-Id antibodies carry an "internal image" of the initial antigen and compete in a dose-dependent manner with Dpt allergens for the binding to the anti-Dpt antibodies and (b) paratope-associated idiotopes of anti-Dpt antibodies are shared by unrelated individuals.

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. III. Cross-reactivity of bystander idiotopes on allergen-specific IgE antibodies.

Rabbits were inoculated with affinity-purified human antibodies to the common house dust mite Dermatophagoides pteronyssinus (DPT) to produce anti-idiotypic (Id) antibodies. The Id carried by human IgE antibodies were studied in a radioimmunoassay in which specific anti-DPT IgE were first insolubilized on rabbit F(ab')2 fragments against human Fc epsilon. In a single individual specific anti-DPT IgE antibodies shared bystander idiotopes (i.e. idiotopes located outside the antigen-binding site) with IgG antibodies of the same specificity, since the adsorption on insolubilized anti-DPT IgG almost completely eliminated the binding of anti-Id antibodies to IgE. This differed from our previous observations (J.-M. R. Saint-Remy et al., Eur. J. Immunol. 1986. 16: 575) wherein distinct paratope-associated idiotopes were identified on IgG and IgE anti-DPT antibodies. The frequency of cross-reactions between idiotopes of anti-DPT IgE antibodies observed in ten unrelated individuals was less than 10% for bystander idiotopes. This finding confirmed the private character of the above idiotopes that we found earlier on anti-DPT IgG antibodies. However, one anti-Id antibody preparation was found to react with bystander idiotopes of anti-DPT IgE of most individuals, thereby suggesting the existence of a recurrent idiotope. The low frequency of inter-individual bystander idiotope cross-reactivity contrasted with the public character of paratope-associated idiotopes.

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. IV. Occurrence of natural autologous anti-idiotypic antibodies.

IgG isolated from the plasma of seven individuals hypersensitive to the common house dust mite Dermatophagoides pteronyssinus (DPT) was exhaustively adsorbed onto insolubilized DPT. The unbound fraction was found by radioimmunoassay to contain antibodies recognizing the variable region of both anti-DPT IgG and IgE antibodies. This recognition was idiotype (Id)-specific as it persisted after passage over insolubilized polyclonal IgG of unrelated specificity. Most of these anti-Id IgG carried the internal image of the initial antigen in that they competitively inhibited the binding of anti-DPT antibodies to DPT. Immunoadsorption of anti-Id IgG onto insolubilized anti-DPT IgG antibodies from the same individual completely eliminated their reaction with anti-DPT IgG but not with anti-DPT IgE, suggesting that idiotopes included in the antigen-binding site of specific IgG and IgE antibodies were not identical. Anti-Id IgG recognizing idiotopes located outside the antigen-binding site (bystander idiotopes) were also completely removed by passage over insolubilized anti-DPT IgG; in this case the reaction of the anti-Id IgG with both anti-DPT IgG and anti-DPT IgE was inhibited, indicating that, for a given individual, bystander idiotopes were shared between anti-DPT antibodies pertaining to these two isotypes.

The human immune response against major allergens from house dust mite, Dermatophagoides pteronyssinus. II. Idiotypic cross-reactions of allergen-specific antibodies.

Antisera were prepared in rabbits against the idiotypic (Id) determinants of antiallergen antibodies. These antibodies were isolated from the plasma of 10 unrelated patients by immunoabsorption. Three major allergens isolated from the house dust mite, Dermatophagoides pteronyssinus (DPT), were used. The anti-Id antisera were rendered specific by successive absorption on insolubilized allergens, IgG and IgM from a pool of human sera and Ig from the donor after removal of anti-DPT antibodies by absorption. Anti-Id antibodies raised essentially against IgG antibodies were found to inhibit the agglutinating activity of both IgG and IgM anti-DPT antibodies toward allergen-coated latex. These anti-Id antibodies were also able to inhibit partly the binding of radiolabeled allergen to IgE anti-DPT antibodies. Matching the anti-Id antisera with the various individual anti-DPT antibodies revealed an Id cross-reactivity of about 71% for IgG, 61% for IgM and 62% for IgE. A second and predominant type of anti-Id antibodies recognized bystander idiotopes as the allergen did not inhibit Id-anti-Id reaction. These idiotopes were apparently more specific to individuals (private) as the anti-DPT antibodies of a given patient did not agglutinate latex particles coated with anti-Id antibodies prepared against Id of another patient.

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. Isotypic analysis of antibodies in atopic and non-atopic subjects.

Specific antibodies isolated by immunoabsorption on four main insolubilized allergens from Dermatophagoides pteronyssinus (DPT) had the following isotypic distribution: in 16 atopic patients, 52% IgG, 40% IgM, 8% IgA, 0.1% IgE and, in 12 non-atopic individuals, 48% IgG, 46% IgM, 6% IgA, 0.03% IgE. The ratios between geometric means of antibody values in each class (atopic vs non-atopics) were 2.4 for IgG, 2.0 for IgM, 2.8 for IgA and 66.7 for IgE. The amount of anti-DPT antibodies in IgG subclasses did not follow the usual distribution of total IgG subclasses, i.e., IgG1 greater than IgG2 greater than IgG3 greater than IgG4. In atopics the order was IgG2 greater than IgG1 greater than IgG4 greater than IgG3 and in non-atopics, IgG4 greater than IgG1 = IgG2 greater than IgG3 although 6/12 of the latter had no detectable (less than 0.5 micrograms/ml plasma) IgG4.