Immunotherapy of hay fever with ragweed antigen E: Comparisons with whole pollen extract and placebos

Norman, Philip S.; Winkenwerder, Walter L.; Lichtenstein, Lawrence M.

doi:10.1016/0021-8707(68)90139-1

Cited by 175 publications

(49 citation statements)

References 11 publications

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“…Part of the difference may be related to the larger amount of antigen given to the children. The clinical response to immunotherapy clearly is dose dependent, and available evidence strongly suggests that relatively high dosage therapy for pollinosis is more likely to produce a favorable clinical result (2). Nonetheless, partial remission still is the rule.…”

Section: Discussionmentioning

confidence: 99%

“…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)(2)(3)(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)(8)(9), and also decreases the in vitro allergen-induced release of histamine from the patients' leukocytes (4,10,11).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunologic and cellular changes accompanying the therapy of pollen allergy

Levy¹,

Lichtenstein²,

Goldstein³

et al. 1971

J. Clin. Invest.

142

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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 ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunologic and cellular changes accompanying the therapy of pollen allergy

Levy¹,

Lichtenstein²,

Goldstein³

et al. 1971

J. Clin. Invest.

142

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“…However, recent evidence suggests that cellular immune responses to ragweed antigen may also be detected (2)(3)(4)(5)(6)(7)(8). In our previous study (2) we measured a broad range of immunologic responses including antigen-induced leukocyte histamine release, the radioallergosorbent test (RAST)1 for specific IgE antiragweed antibody (IgEAR), lymphocyte proliferation, and the production of two lymphocyte mediators, migration inhibitory factor (MIF) and mitogenic factor (MF).…”

Section: Introductionmentioning

confidence: 99%

The effect of immunotherapy on humoral and cellular responses in ragweed hayfever.

Evans¹,

Pence²,

Kaplan³

et al. 1976

J. Clin. Invest.

140

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A B S T R A C T The effect of specific immunotherapy on several in vitro responses to ragweed antigen E has been evaluated in 17 atopic patients with ragweed hayfever. The methods employed were leukocyte histamine release, measurement of specific IgE anti-ragweed antibody and specific IgG anti-ragweed antibody, lymphocyte proliferation, and the production of two lymphocyte mediators (migration inhibitory factor and mitogenic factor). The duration of treatment and symptom improvement were also recorded for comparison.Immunotherapy was associated with a decrease in leukocyte sensitivity for histamine release to ragweed antigen E in a majority of the patients. In addition, there was a significant decrease in IgE anti-ragweed antibody and a significant increase in IgG anti-ragweed antibody. Immunotherapy also resulted in a significant decrease in lymphocyte responsiveness to ragweed antigen E as measured by proliferation and the production of mediators. Symptomatic improvement was best correlated with the presence of IgG anti-ragweed antibody responses. The production of this antibody was also associated with a decrease in lymphocyte responsiveness. The results of this study indicate that specific immunotherapy in ragweed-sensitive patients induces alterations in immunologic reactivity to ragweed antigen in vitro. This response is antigen specific, includes elements of both humoral and cellular immunity, and may account

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“…Variability in the composition of such extracts is a problem inherent in biological products. Purified major allergens were already proposed and tested as alternatives for those extracts several decades ago [25, 26]. Although molecular biology has facilitated the production of recombinant versions of major allergens, recombinant products are not yet available on the market to replace current extract-based products.…”

Section: Introductionmentioning

confidence: 99%

The Major Grass Pollen Group 5 Allergen from <i>Dactylis glomerata </i>and Its C-Terminal Split Product Both Behave as Dimers: Implications for Allergen Standardization

Oort

Dieker

Heer

et al. 2005

Int Arch Allergy Immunol

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Background: On SDS-PAGE grass pollen group-5 allergens migrate as a doublet with an apparent molecular mass (M_r) of 25 kDa. Immunoblot analysis revealed additional group 5 reactivity at double and half this M_r. The aim of this study was to investigate these group 5 molecular entities and to compare their allergenicity and behavior in quantitative immunoassays. Methods: Group-5-specific monoclonal antibodies were produced and used for the development of a group-5-specific sandwich ELISA. Affinity-purified Dac g 5 was separated by SDS-PAGE/Western blotting; individual bands were analyzed by N-terminal sequencing. Size exclusion chromatography (SEC) in conjunction with group-5-specific ELISA, competitive RIA and RAST inhibition were used to analyze the size distribution of Dac g 5. Basophil histamine release assays were used to assess biological activity. Results: The lower band of the typical group 5 doublet was identified as a truncated form lacking the typical group 5 N-terminus AD^L/_AGY, observed in the upper band. The 12-kDa peptide was shown to be the C-terminal half of Dac g 5 (amino acid 127 onwards). SEC in conjunction with competitive RIA revealed that around 45% of Dac g 5 is represented by the 12-kDa peptide. Both the C-terminal half and the whole allergen dimerize under nondenaturing conditions. In competitive RIA and RAST inhibition both forms are equally well detected. In contrast, the half molecule is poorly recognized in sandwich ELISA and displays negligible biological activity in basophil histamine release tests with purified IgE. Conclusions: These observations stress the need to evaluate the performance of allergen standardization protocols in detail, with special attention to allergen size distribution.

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Immunotherapy of hay fever with ragweed antigen E: Comparisons with whole pollen extract and placebos

Cited by 175 publications

References 11 publications

Immunologic and cellular changes accompanying the therapy of pollen allergy

Immunologic and cellular changes accompanying the therapy of pollen allergy

The effect of immunotherapy on humoral and cellular responses in ragweed hayfever.

The Major Grass Pollen Group 5 Allergen from <i>Dactylis glomerata </i>and Its C-Terminal Split Product Both Behave as Dimers: Implications for Allergen Standardization

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