Immunologic and cellular changes accompanying the therapy of pollen allergy

Abstract

A B S T R A C T We had found previously that children with ragweed hay fever were somewhat less symptomatic after preseasonal immunization with large doses of ragweed pollen extract than were placebo-treated children. To study further the immunologic changes which accompany immunotherapy, these children were treated again the following year. Each patient served as his own control.Serum blocking (IgG) antibody, measured by inhibition of antigen-induced leukocyte histamine release, was increased 20-to 40-fold after therapy. The anticipated postpollen season increase of serum reaginic (IgE) antibody, measured by passive sensitization of leukocytes from nonallergic donors, was suppressed. Instead, the mean titer was decreased after treatment. Total serum IgE levels, measured by radial radioimmunodiffusion assay, were higher than normal; were correlated with reaginic antibody titers; and also did not increase in the pollen season after treatment. The concentration of both IgE and reaginic antibody was lower in the older children, irrespective of treatment.Leukocyte response to ragweed antigen E and guinea pig anti-IgE antiserum was assessed by means of in vitro histamine release techniques. After treatment, the leukocytes of 21 patients were less sensitive (11 cases), or less reactive (10 cases), to antigen E. Response to anti-IgE antibody also was diminished after treatment. In four cases, neither anti-IgE nor antigen E induced histamine release, although both IgE protein and ragweed-specific IgE antibody were present in the patients' own sera. Clinical improvement was correlated best with decreased leukocyte sensitivity and leukocyte reactivity to ragweed antigen E. It appeared that decreased cell sensitivity was related to lower serum reaginic antibody levels. Decreased cell reactivity, in the presence of both IgE protein and IgE antibody in the serum, may indicate a change in cellular response mechanisms. These studies suggest that clinical improvement following specific immunotherapy must be the result of complex changes in the immunologic and cellular components of allergic disease. INTRODUCTIONImmunotherapy has long been the major form of treatment for pollen allergy. In recent controlled studies, it has been shown to result in at least partial amelioration of the symptoms of hay fever in adults and children (1-4). Previous studies of the immunologic parameters of pollinosis have demonstrated that immunization with pollen allergen stimulates the production of blocking antibody (5, 6), reduces the serum titer of reaginic antibody (7-9), and also decreases the in vitro allergen-induced release of histamine from the patients' leukocytes (4, 10, 11).In recent studies, reaginic antibodies, which are responsible for the sensitivity of allergic individuals to specific allergens, have been identified as IgE immunoglobulins (12). Immunoglobulins of this class are present in the serum and on the histamine-containing cells of both allergic and nonallergic individuals. The mean concentration of IgE in serum from allergic ...

Seasonal Changes in IgE Antibodies and Their Relationship to IgG Antibodies during Immunotherapy for Ragweed Hay Fever

“…5 (6,7,23). The difference in our fesults and those in earlier studies may be due to differences in the methods used to measure IgE antibody activity, or possibly to differences in the study groups; most of the subjects studied earlier were children (6,7).…”

“…In addition to its relative technical simplicity, RAST would appear to be more sensitive than passive leukocyte sensitization for detection of IgE antibodies (6), in that IgE antibody can be measured by the latter method in the serum of only half of adult patients with ragweed hay fever. Finally, the solid-phase ragweed antigen was remarkably stable, and even after storage for 1 yr at 4VC in the RAST buffer, its reactivity with a standard serum was essentially unchanged.…”

“…These IgE antibodies may be measured in vitro by coprecipitation with radiolabeled antigen (3), by passive leukocyte sensitization (4) or by the radioallergosorbent test (RAST)1 (5). With passive leukocyte sensitization, IgE antibodies can be readily measured in the serums of children with ragweed hay fever, whereas IgE antibodies are detectable in only about 50% of adult patients with this method (6,7).…”

“…After the ragweed pollination season, IgE antibodies in serum increase in concentration, and in children this increase appears to be partially suppressed by immunotherapy (6). Cells of the treated subjects become less sensitive or less reactive to ragweed antigen E (AgE) (6,7), and IgG antibodies ("blocking" antibodies) appear in the serum (8)(9)(10).…”

“…Cells of the treated subjects become less sensitive or less reactive to ragweed antigen E (AgE) (6,7), and IgG antibodies ("blocking" antibodies) appear in the serum (8)(9)(10). The apparent suppression of IgE antibody has been attributed to the presence of IgGblocking antibody (6).…”