We have prepared antigen-antibody complexes from grass pollen allergens and autologous specific antibodies isolated by immunoadsorption from the serum of allergic patients. These complexes were inoculated into patients in a double-blind trial to evaluate their effect on grass pollen-related rhinitis and bronchial asthma. Thirty-eight grass pollen-hypersensitive patients were allocated to three groups; patients in the first two groups were treated with antigen-antibody complexes at different ratios and dosages and were compared with the third group who received the placebo carrier buffer alone. In addition, we treated a fourth group who had already received antigen-antibody complex inoculation during the previous pollen season. Injections were given every 2 weeks during the pollen season, starting 5 weeks prior to it. Tolerance was excellent with no signs of local or systemic side effects. The treatment prevented nasal symptoms while enabling the patients to reduce antihistamine intake. Bronchial asthma was virtually absent in the treated groups even though no bronchodilators or corticosteroids had to be taken. Specific IgE antibodies did not increase during the pollen season nor did IgG "blocking" antibodies. Inoculation of allergen-antibody complexes could provide a valuable alternative for the treatment of immediate hypersensitivity to airborne allergens as it appears to be safe and rapidly efficacious. This treatment offers several advantages compared to conventional hyposensitization and is characterized by the absence of an increase in specific IgG antibodies.
Atopic dermatitis (AD) can be exacerbated by contact with airborne allergens, amongst which Dermatophagoides pteronyssinus (Dpt) appears to be potentially important. Specific IgE antibodies towards Dpt are often found in AD and it can therefore be speculated that suppression of the production of anti-Dpt IgE might result in a significant clinical improvement. Complexes of antigen and specific antibodies have been shown to suppress the production of antibody in other systems; we report here the evaluation in an open trial of the capacity of such complexes to improve symptoms of AD. Ten adult patients were enrolled in this study. In addition to satisfying the criteria of AD, they all suffered from a severe disease (more than 20% of the body surface involved) that had been stable for at least the last 2 years. The patients had high titers of total IgE antibodies and specific anti-Dpt antibodies. Allergen-antibody complexes were prepared from Dpt allergens and an excess of autologous specific anti-Dpt antibodies obtained by immunoadsorption. The patients received regular injections of these complexes throughout 1 year, during which clinical parameters of disease intensity, percentage of body surface affected and intensity of pruritus were regularly monitored. A significant clinical improvement was obtained after 3–4 months of therapy and was maintained through the 9th month. After 1 year of treatment 2 patients were completely free of disease 4 had residual lesions which continued to improve and 4 patients had a partial recurrence of dermatitis. In addition to the demonstration that injection of antigen-antibody complexes results in a clinical benefit, these results suggest that the immune response towards Dpt is a relevant factor in AD.
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.
This study describes the long-term follow-up of the clinical response of 10 adult patients suffering from atopic dermatitis (AD) who were treated by administration of complexes made of Dermatophagoidespteronyssinus (Dpt) allergens and autologous antibodies specific to that allergen. We have already described the clinical improvement observed after 1 year of treatment involving regular injections of complexes; this improvement was maintained throughout a second year, even though the number of injections was greatly reduced. At the end of the second year of treatment, 5 patients were completely free of disease, and 3 had had a short-lasting recurrence of low-severity dermatitis. Using a disease intensity index the mean improvement for these 8 patients was 83% compared to baseline values. One patient showed a significant recurrence of symptoms, and 1 patient left the study for personal reasons when she was in good clinical condition. A significant reduction of specific anti-Dpt IgE antibody titers was observed in 7 out of the 8 patients in clinical remission, while the level of total IgE antibodies was unchanged until the very end of the study. This study not only confirms that clinical benefit can be obtained from the treatment of AD patients hypersensitive to Dpt by injections of allergen-antibody complexes but also indicates that the therapy induces a suppression of IgE antibody production that is specific for the particular allergen.
Summary Symptoms of atopic dermatitis (AD) can be provoked by exposure to airborne allergens. We have previously shown that patients hypersensitive to D. pteronyssinus (Dpt) allergens were improved by administration of complexes composed of specific antibodies and allergen, which reduce the allergen‐specific immune response. We now report that similar results can be achieved by using F(ab′)2 fragments of specific antibodies instead of whole antibody molecules. Eight adult patients with severe AD were included in a single‐blind study. During the first 11 months patients were maintained on injections of carrier buffer alone, in an effort to evaluate the extent of spontaneous improvement. They were then treated with intradermal injections of allergen‐F(ab′)2 complexes made from autologous specific antibodies and Dpt allergens. The majority of the patients improved spontaneously during the summer months, with an average 30% reduction of symptoms. However, a much more pronounced improvement was observed after 3 months on active therapy, corresponding to a cumulative amount of 60 μg F(ab′)2 and 15 μg allergens. The patients continued to improve over the next 5 months, showing an average 83% reduction of severity scores. The use of F(ab′)2 antibody fragments reduces the risk of inducing an anti‐allotypic immune response, and raises the possibility of adding adjuvants to allergen‐antibody complexes and/or using specific antibodies isolated from pooled gammaglobulins.
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