Irena M. Suszko

A double-blind, placebo-controlled trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Immunotherapy with polymerized ragweed (PRW) has been demonstrated to be safe and effective when compared with monomeric ragweed or untreated controls. To further establish the efficacy of PRW, a trial was conducted comparing PRW, placebo, and no treatment in ragweed-sensitive individuals. In a double-blind manner, 21 patients were treated before the 1981 ragweed season with 15 weekly injections of PRW totaling about 50,000 PNU and 1200 microgram antigen E, while 19 patients were treated with 15 weekly injections of a caramelized glucose and histamine placebo. An additional control group received no injections. Blood was drawn for IgE against ragweed antigen E (IgE-a-AgE) and for blocking antibody against AgE before treatment, after treatment (before season), and after season. In the untreated patients, blood was drawn before season and after season. Daily symptom score sheets were completed by patients each day of the ragweed season. Blocking antibody rose more than 40-fold with treatment (p = 0.0001) in the PRW group but was unchanged in the placebo group with treatment. IgE-a-AgE rose with PRW therapy. Clinical efficacy of PRW was again confirmed in this study. Symptom score mean in the PRW group was statistically lower than the mean in the placebo group (p = 0.022) and in the untreated group (p = 0.018). There were no systemic reactions and only minor local reactions during treatment. In summary, PRW is an improved form of immunotherapy.

A double-blind histamine placebo—controlled trial of polymerized whole grass for immunotherapy of grass allergy

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group (p less than 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 +/- 71 (S.E.M.), statistically lower (p less than 0.02) than the mean in the placebo group 496 +/- 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

Persistence of efficacy after a brief course of polymerized ragweed allergen: A controlled study☆

Immunotherapy with PRW has been demonstrated to be safe and effective. To determine whether the efficacy would remain in successive ragweed seasons without further therapy, a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously. Those patients were also compared to previously untreated ragweed-sensitive patients. In a double-blind fashion, 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy, whereas 21 previously treated patients were treated with four injections of placebo therapy. An additional control group of 21 previously untreated ragweed-sensitive patients received no injections. Daily symptom and medication score sheets were completed by patients each day of the ragweed season. Blocking antibody rose elevenfold with treatment (p less than 0.0001) in the PRW group. There was a statistically significant difference in symptom score mean between untreated patients (1007 +/- 174) and previously treated patients whether they received supplemental injections (554 +/- 180) (p less than 0.01) or whether they did not (650 +/- 168) (p less than 0.03). In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy.

Respiratory Mast Cells and Basophiloid Cells

The content of 3′,5′-adenosine monophosphate (cAMP) in free bronchial respiratory cells (RC) from dogs and rhesus monkeys was determined and compared with that of human peripheral blood leukocytes. Th

Comparison of immune reactivity to polyvalent monomeric and polymeric ragweed antigens

The proteins of an aqueous extract of ragweed pollen (RW) were precipitated at 90% saturation with (NH4)2SO4, solubilized, and sieved through Sephadex G-15. The excluded fraction, termed the monomeric form (MRW), was cross-linked with glutaraldehyde to form polymerized ragweed (PRW). As compared with MRW, PRW is more immunogenic in rabbits in the production of antibody against RW antigen E (AgE). MRW and PRW resulted in equal peak reaginic responses in rabbits but the duration of reagin production was longer after immunization with MRW than with PRW. Both MRW and PRW have exposed antigenic determinants of AgE but PRW had approximately 1/3 the number as shown by neutralization of human antibody against RW AgE. PRW had 100-to 1,000-fold less human cutaneous reactivity than MRW. PRW may be a more easily effective therapeutic agent for human RW immunotherapy than currently used aqueous extracts and may be more readily obtainable than polymerized AgE.

A multi-institutional trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Abstract Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.

Polymerized whole ragweed: An improved method of immunotherapy

A single-blind study compared the effectiveness of glutaraldehyde-treated polymerized ragweed with nonpolymerized monomeric ragweed. These studies are an extension of those previously reported for polymerized AgE using a readily available ragweed preparation containing all ragweed antigens. Nineteen ragweed-sensitive patients were randomized into 2 groups; 10 received the polymerized form and 9 received the monomeric form. Four parameters were followed: serum-specific IgE against antigen E, total blocking antibody against antigen E, local and systemic reactions to injection therapy, and symptom score indices. Pretreatment levels of antigen E--specific IgE and blocking antibody activity were similar in both groups. After a total of 15,000 protein nitrogen units (PNU) had been given, blocking antibody activity in the monomer group rose from a mean of 170 ng AgE bound per ml to a mean of 2,813. The rise in blocking antibody activity in the polymer group was from a mean of 181 ng AgE bound per ml to 1,574. At 15,000 PNU, blocking antibody activity levels were not statistically different in the 2 groups. After 1 year of treatment, no consistent decrease in postseasonal specific IgE rise could be shown in either group. Forty times less erythema and 15 times less induration were found with polymerized ragweed. There were 7 systemic reactions with the monomer and none with the polymer. Both groups experienced symptomatic improvement with treatment.

Polymerization of mixtures of grass allergens

Mixed grass pollen allergens were precipitated from crude grass extract by 90% saturation with ammonium sulfate. The precipitate was dissolved and polymerized with glutaraldehyde. Polymerized allergens with a molecular weight range of 200,000 to 4,000,000 were isolated. The resultant grass allergen polymers had reduced allergenicity but were capable of absorbing out IgG antibody from sera of 2 patients treated with crude grass allergens. This alteration of allergenicity was intended to reduce the ability of allergens to react with IgE-sensitized cells rather than to modify or destroy antigenic determinants. Prior exposure of allergens to phenol used as a preservative inhibited the polymerization process probably by blocking combining sites with which glutaraldehyde reacts.

Reduced allergenicity of high molecular weight ragweed polymers

Polymerized ragweed antigens of different molecular weight ranges were studied to determine if the degree of allergenicity was dependent on molecular size of the polymers. In this study, allergenicity is defined as the ability to elict IgE-mediated skin reactivity. Ragweed antigen treated with glutaraldehyde was fractionated into one preparation with a molecular weight range of 200,000 to 20,000,000 and another with molecular weights less than 200,000. Except for the difference in molecular sizes of the two molecular sizes of the two preparations, all ragweed polymers had been treated in an identical fashion. The low molecular weight fraction had cutaneous endpoint reactivity greater than 10(5) to 10(8) times that of the high molecular weight materials. In these and other studies, immunogenicity defined as the ability to induce an IgG antibody response was retained by the high molecular weight material. The results are consitent with the hypothesis that allergenicity decreases as the molecular weight of the polymerized allergen increases.

Polymerized whole ragweed: Human safety and immune response

Abstract Polymerized ragweed (PRW) has been shown to have reduced allergenicity while maintaining immunogenicity. In order to evaluate whether the reduced allergenicity would permit high initial doses and rapid progression to maintenance, two groups of subjects with ragweed pollenosis were placed on immunotherapy with PRW standardized for antigen E (AgE) content. Group I, 28 subjects, received an initial dose of 100 protein nitrogen units (PNU) (1 μg AgE) and reached a maintenance dose of 1,000 PNU (10 μg AgE) in four weekly injections. In the first 10 wk each subject received 7,850 PNU (78.5 μg AgE). Group II, six subjects, received an initial dose of 100 PNU (1 μg AgE) and after 11 weekly injections received 30,000 PNU (300 μg AgE). No anaphylactic reactions occurred in the study groups. In group I, three large immediate-type local reactions and nine large late-type reactions occurred in 110 injections. Anti-AgE antibody activity in group I rose from a pretreatment mean value of 264 ng AgE bound per milliliter serum to a posttreatment value of 3,182. The major rise occurred after only 4 wk of therapy. In group II, anti-AgE antibody activity rose from 66 to 2,123 after the 11 wk of therapy. IgE antibody to AgE did not change to any extent in either group, and histamine release in response to AgE measured in group II patients did not change. Symptom score evaluation of group I patients revealed a marked decrease in symptoms after therapy with PRW. Immunotherapy with PRW can be initiated at higher doses, with rapid attainment of maintenance dosage with safety resulting in a brisk immune response and symptomatic improvement.